Methods and systems for treatment of acute ischemic stroke

ABSTRACT

A system of devices for treating an artery includes an arterial access sheath adapted to introduce an interventional catheter into an artery and an elongated dilator positionable within the internal lumen of the sheath body. The system also includes a catheter formed of an elongated catheter body sized and shaped to be introduced via a carotid artery access site into a common carotid artery through the internal lumen of the arterial access sheath. The catheter has an overall length and a distal most section length such that the distal most section can be positioned in an intracranial artery and at least a portion of the proximal most section is positioned in the common carotid artery during use.

REFERENCE TO PRIORITY DOCUMENTS

This application is a Continuation of co-pending U.S. patent applicationSer. No. 15/699,401, filed Sep. 8, 2017, which is a continuation of U.S.patent application Ser. No. 15/425,460, filed on Feb. 6, 2017, now U.S.Pat. No. 10,471,233, which is a continuation of U.S. patent applicationSer. No. 14/576,953 filed on Dec. 19, 2014 now U.S. Pat. No. 9,561,345,and claims priority to (1) U.S. Provisional Patent Application Ser. No.61/919,945, filed Dec. 23, 2013, entitled “Methods and Systems forTreatment of Acute Ischemic Stroke”; (2) U.S. Provisional PatentApplication Ser. No. 62/083,128, filed Nov. 21, 2014, entitled “Methodsand Systems for Treatment of Acute Ischemic Stroke”; (3) U.S.Provisional Patent Application Ser. No. 62/029,799, filed Jul. 28, 2014,entitled “Intravascular Catheter with Smooth Transitions ofFlexibility”; (4) U.S. Provisional Patent Application Ser. No.62/075,101, filed Nov. 4, 2014, entitled “Transcarotid NeurovascularCatheter”; (5) U.S. Provisional Patent Application Ser. No. 62/046,112,filed Sep. 4, 2014, entitled “Methods and Devices for TranscarotidAccess”; and (6) U.S. Provisional Patent Application Ser. No.62/075,169, filed Nov. 4, 2014, entitled “Methods and Devices forTranscarotid Access.” The disclosures of the patent applications areincorporated by reference in their entirety and priority to the filingdates is claimed.

BACKGROUND

The present disclosure relates generally to medical methods and devicesfor the treatment of acute ischemic stroke. More particularly, thepresent disclosure relates to methods and systems for transcarotidaccess of the cerebral arterial vasculature and treatment of cerebralocclusions.

Acute ischemic stroke is the sudden blockage of adequate blood flow to asection of the brain, usually caused by thrombus or other emboli lodgingor forming in one of the blood vessels supplying the brain. If thisblockage is not quickly resolved, the ischemia may lead to permanentneurologic deficit or death. The timeframe for effective treatment ofstroke is within 3 hours for intravenous (IV) thrombolytic therapy and 6hours for site-directed intra-arterial thrombolytic therapy orinterventional recanalization of a blocked cerebral artery. Re-perfusingthe ischemic brain after this time period has no overall benefit to thepatient, and may in fact cause harm due to the increased risk ofintracranial hemorrhage from fibrinolytic use. Even within this timeperiod, there is strong evidence that the shorter the time periodbetween onset of symptoms and treatment, the better the results.Unfortunately, the ability to recognize symptoms, deliver patients tostroke treatment sites, and finally to treat these patients within thistimeframe is rare. Despite treatment advances, stroke remains the thirdleading cause of death in the United States.

Endovascular treatment of acute stroke is comprised of either theintra-arterial administration of thrombolytic drugs such as recombinanttissue plasminogen activator (rtPA), mechanical removal of the blockage,or a combination of the two. As mentioned above, these interventionaltreatments must occur within hours of the onset of symptoms. Bothintra-arterial (IA) thrombolytic therapy and interventional thrombectomyinvolve accessing the blocked cerebral artery via endovasculartechniques and devices.

Like IV thrombolytic therapy, IA thrombolytic therapy alone has thelimitation in that it may take several hours of infusion to effectivelydissolve the clot. Mechanical therapies have involved capturing andremoving the clot, dissolving the clot, disrupting and suctioning theclot, and/or creating a flow channel through the clot. One of the firstmechanical devices developed for stroke treatment is the MERCI RetrieverSystem (Concentric Medical, Redwood City, Calif.). A balloon-tippedguide catheter is used to access the internal carotid artery (ICA) fromthe femoral artery. A microcatheter is placed through the guide catheterand used to deliver the coil-tipped retriever across the clot and isthen pulled back to deploy the retriever around the clot. Themicrocatheter and retriever are then pulled back, with the goal ofpulling the clot, into the balloon guide catheter while the balloon isinflated and a syringe is connected to the balloon guide catheter toaspirate the guide catheter during clot retrieval. This device has hadinitially positive results as compared to thrombolytic therapy alone.

Other thrombectomy devices utilize expandable cages, baskets, or snaresto capture and retrieve clot. Temporary stents, sometimes referred to asstentrievers or revascularization devices, are utilized to remove orretrieve clot as well as restore flow to the vessel. A series of devicesusing active laser or ultrasound energy to break up the clot have alsobeen utilized. Other active energy devices have been used in conjunctionwith intra-arterial thrombolytic infusion to accelerate the dissolutionof the thrombus. Many of these devices are used in conjunction withaspiration to aid in the removal of the clot and reduce the risk ofemboli. Frank suctioning of the clot has also been used withsingle-lumen catheters and syringes or aspiration pumps, with or withoutadjunct disruption of the clot. Devices which apply powered fluidvortices in combination with suction have been utilized to improve theefficacy of this method of thrombectomy. Finally, balloons or stentshave been used to create a patent lumen through the clot when clotremoval or dissolution was not possible.

SUMMARY

Disclosed are methods and devices that enable safe, rapid and relativelyshort transcarotid access to the cerebral and intracranial arteries totreat acute ischemic stroke. The methods and devices include one or moretranscarotid access devices, catheters, and thrombectomy devices toremove the occlusion. Methods and devices are also included to provideaspiration and passive flow reversal for the purpose of facilitatingremoval of the occlusion as well as minimizing distal emboli. The systemoffers the user a degree of flow control so as to address the specifichemodynamic requirements of the cerebral vasculature. The disclosedmethods and devices also include methods and devices to protect thecerebral penumbra during the procedure to minimize injury to brain. Inaddition, the disclosed methods and devices provide a way to securelyclose the access site in the carotid artery to avoid the potentiallydevastating consequences of a transcarotid hematoma.

In one aspect, there is disclosed a system of devices for treating anartery, comprising: an arterial access sheath adapted to introduce aninterventional catheter into an artery, the arterial access sheathincluding a sheath body sized and shaped to be introduced into a commoncarotid artery via a carotid artery access site, the sheath bodydefining an internal lumen that provides a passageway for introducing acatheter into the common carotid artery when the first elongated body ispositioned in the common carotid artery, wherein the sheath body has aproximal section and a distalmost section that is more flexible than theproximal section, and wherein a ratio of an entire length of thedistalmost section to an overall length of the sheath body is one tenthto one half the overall length of the sheath body; an elongated dilatorpositionable within the internal lumen of the sheath body, wherein thearterial access sheath and the dilator can be collectively introducedinto the common carotid artery; and a catheter formed of an elongatedcatheter body sized and shaped to be introduced via a carotid arteryaccess site into a common carotid artery through the internal lumen ofthe arterial access sheath, the catheter body sized and shaped to benavigated distally to a intracranial artery through the common carotidartery via the access location in the carotid artery, wherein thecatheter body has a length of 40 cm to 70 cm, and wherein the catheterbody has a proximal most section and a distal most section wherein theproximal most section is a stiffest portion of the catheter body, andwherein the catheter body has an overall length and a distal mostsection length such that the distal most section can be positioned in anintracranial artery and at least a portion of the proximal most sectionis positioned in the common carotid artery during use.

Other features and advantages should be apparent from the followingdescription of various embodiments, which illustrate, by way of example,the principles of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary embodiment of a system of devices fortranscarotid access and treatment of acute ischemic stroke showing anarterial access device inserted directly into the carotid artery and acatheter.

FIG. 2 illustrates another embodiment of a system of devices fortranscarotid access and treatment of acute ischemic stroke with aballoon-tipped arterial access device and a thrombectomy device.

FIG. 3 illustrates another embodiment of a system of devices fortranscarotid access and treatment of acute ischemic stroke with aballoon-tipped guide catheter.

FIG. 4 shows an embodiment of a transcarotid initial access system.

FIG. 5 shows an embodiment of a transcarotid access sheath system.

FIGS. 6-11 show embodiments of a transcarotid arterial access sheath.

FIG. 12 shows an embodiment of an arterial access device which has twoocclusion balloons and an opening between the two balloons

FIG. 13 shows an embodiment of a telescoping arterial access device.

FIGS. 14a and 14b show embodiments of an arterial access device with asheath stopper.

FIGS. 15-18 shows an example of an arterial access device comprised of asheath that has an expandable distal tip.

FIGS. 19-21 show embodiments of dilators.

FIGS. 22-23 show embodiments of catheters.

FIGS. 24 A-D show examples of catheters having non-square distal tips ordistal edges.

FIGS. 25A and 25B show examples of catheters and tapered dilators in anartery.

FIG. 26 shows an example of a microcatheter with an anchor device.

FIG. 27 shows a guidewire with an anchor device.

FIG. 28 shows a catheter and an arterial access device combined in asingle device.

FIGS. 29 and 30 show a catheter having a pair of lumens.

FIGS. 31A-31C show a telescopic catheter and arterial sheath system.

FIGS. 32-35 show examples of systems for treating an artery with activeaspiration.

FIGS. 36 and 37 shows cross-sectional views of aspiration pump devices.

FIG. 38 shows an exemplary embodiment of a system that uses venousreturn to establish passive retrograde flow into the arterial accessdevice.

FIG. 39 shows an exemplary thrombectomy device.

FIG. 40 shows a microcatheter that includes at least two lumens.

FIGS. 41-42 illustrates embodiments of a distal perfusion catheter.

FIGS. 43-45 illustrate different embodiments of distal perfusioncatheters with an occlusion balloon.

FIG. 46 shows a distal region of a perfusion catheter with an expandabledevice.

FIG. 47 shows a proximal perfusion catheter being deployed distal of theocclusion via the arterial access device or catheter.

FIGS. 48A-48D illustrates steps in usage of a distal balloon catheterconfigured to perfuse distal and/or proximal to the balloon.

FIGS. 49-50 shows an embodiment of an arterial access system whichfacilitates usage of a vessel closure device.

FIGS. 51-53 show thrombus disruption devices.

FIGS. 54-57 show tables containing data related to the devices disclosedherein.

DETAILED DESCRIPTION

Interventions in the cerebral or intracranial vasculature often havespecial access challenges. Most neurovascular interventional proceduresuse a transfemoral access to the carotid or vertebral artery and thenceto the target cerebral or intracranial artery. In recent years,interventional devices such as wires, guide catheters, stents andballoon catheters, have all been scaled down and been made more flexibleto better perform in the neurovascular anatomy. Currently, access andtreatment catheters to treat stroke range in length from 105 to 135 cmin length, with microcatheters up to 150 cm in length. These cathetersaccess the arterial system from the femoral artery and must navigate theaortic arch and cervical and intracranial arteries to reach theocclusion in the cerebral artery. The access route is long, oftentortuous and may contain stenosis plaque material in the aortic arch andcarotid and brachiocephalic vessel origins, presenting a risk of emboliccomplications during the access portion of the procedure. In patientswith tortuous anatomy, access to the occlusion may be difficult orimpossible with existing catheters and devices. In addition, thecerebral vessels are usually more delicate and prone to perforation thancoronary or other peripheral vasculature. Many neurovascularinterventional procedures remain either more difficult or impossiblebecause of device access challenges.

One severe drawback to current acute stroke interventions is the amountof time required to restore blood perfusion to the brain, which can bebroken down to time required to access to the blocked cerebral artery,and time required to restore flow through the occlusion. Restoration offlow, either through thrombolytic therapy, mechanical thrombectomy, orother means, often takes hours during which time brain tissue isdeprived of adequate oxygen. During this period, there is a risk ofpermanent injury to the brain tissue. In the setting of acute ischemicstroke where “time is brain,” these extra difficulties have asignificant clinical impact.

Another challenge of neurovascular interventions is the risk of cerebralemboli. In order to reach cerebral vessels from a transfemoral accesssite, catheters must traverse peripheral arteries, the aortic arch, andthe carotid arteries. In many patients, there is disease in the form ofatherosclerosis in these arteries. Navigating catheters across thesearteries may cause fragments to break off and flow to the brain, causingcerebral emboli. Often these emboli lead to procedure-related strokes,but even sub-clinical embolic burdens to the brain have been known tolead to altered mental states.

Once a target site has been reached, there is still a risk of cerebralemboli. During the effort to remove or dissolve clot blockages in thecerebral artery, for example, there is a significant risk of thrombusfragmentation creating embolic particles which can migrate downstreamand compromise cerebral perfusion, leading to neurologic events. Incarotid artery stenting procedures CAS, embolic protection devices andsystems are commonly used to reduce the risk of embolic material fromentering the cerebral vasculature. The types of devices includeintravascular filters, and reverse flow or static flow systems.Unfortunately, because of the delicate anatomy and access challenges aswell as the need for rapid intervention, these embolic protectionsystems are not used in interventional treatment of acute ischemicstroke.

Some of the current mechanical clot retrieval procedures for stroketreatment use aspiration as a means to reduce the risk of emboli andfacilitate the removal of the clot. For example, some clot retrievalprocedures include attaching a large syringe to the guide catheter, andthen blocking the proximal artery and aspirating the guide catheterduring pull back of the clot into the guide. The guide catheter may ormay not have an occlusion balloon. However, this step requires a secondoperator, may require an interruption of aspiration if the syringe needsto be emptied and reattached, and does not control the rate or timing ofaspiration. This control may be important in cases where there is somequestion of patient tolerance to reverse flow. Furthermore, there is noprotection against embolic debris during the initial crossing of theclot with the microcatheter and deployment of the retrieval device.Aspiration devices such as the Penumbra System utilize catheters whichaspirate at the face of the clot while a separate component is sometimesadditionally used to mechanically break up the clot. Aspiration methodsand devices can have the potential to more rapidly restore flow andreduce the level of distal emboli, as there is no requirement to crossor disrupt the clot to remove it. However, the efficacy of aspirationwith current catheter designs is limited and often requires multipleattempts and/or adjunct mechanical thrombectomy devices, thusdiminishing the time and reduced distal emboli benefits.

Disclosed are methods and devices that enable safe, rapid and relativelyshort and straight transcarotid access to the carotid arteries andcerebral vasculature for the introduction of interventional devices fortreating ischemic stroke. Transcarotid access provides a short lengthand non-tortuous pathway from the vascular access point to the targetcerebral vascular treatment site, thereby easing the time and difficultyof the procedure, compared for example to a transfemoral approach.Additionally, this access route reduces the risk of emboli generationfrom navigation of diseased, angulated, or tortuous aortic arch orcarotid artery anatomy. Further, this access route may make some or allaspects of the procedure faster, safer, and more accurate, as describedin more detail below. The devices and associated methods includetranscarotid access devices, guide catheters, catheters, and guide wiresspecifically to reach a cerebral target anatomy via a transcarotidaccess site, and associated stroke treatment devices which have beenoptimized for delivery through a transcarotid access site also known asa transcervical access site.

Disclosed also are methods and devices to provide aspiration and passiveflow reversal either from the access sheath, a guide catheter, or acatheter for the purpose of minimizing distal emboli. Disclosed also aremethods and devices that optimize clot aspiration through eithertransfemoral or transcarotid access approaches. Included in thisdisclosure are kits of various combinations of these devices tofacilitate transcarotid neurovascular interventional procedures.

In another aspect, there is disclosed methods and devices foradditionally providing active aspiration as well as passive retrogradeflow during the procedure to minimize distal emboli. The system offersthe user a degree of blood flow control so as to address the specifichemodynamic requirements of the cerebral vasculature. The system mayinclude a flow controller, which allows the user to control the timingand mode of aspiration.

FIG. 1 shows a system of devices for accessing the common carotid artery(CCA) via a transcarotid approach and for delivering devices to thecerebral vasculature, for example an occlusion 10 in the cerebralartery. The system includes an arterial access device 2010 (sometimesreferred to herein as an arterial access sheath) having an internallumen and a port 2015. The arterial access device 2010 is sized andshaped to be inserted into the common carotid artery via a transcarotidincision or puncture and deployed into a position that provides accessto the cerebral vasculature, for example the common or internal carotidartery. The port 2015 provides access to the arterial access device'sinternal lumen, which is configured for introducing additional devicesinto the cerebral vasculature via the arterial access device 2010.

FIG. 2 shows an alternate system embodiment, in which the arterialaccess device has an occlusion balloon 2020 that occludes the artery atthe position of the sheath distal tip. As shown, the sheath is longenough to reach the distal cervical ICA from the transcarotid accesssite, but other embodiments may be shorter such that the occlusionballoon 2020 positioned in the CCA.

In an embodiment, transcarotid access to the common carotid arterydirectly with the arterial access device 2010 is achieved percutaneouslyvia an incision or puncture in the skin. In an alternate embodiment, thearterial access device 2010 accesses the common carotid artery CCA via adirect surgical cut down to the carotid artery. In another embodiment,the arterial access device provides access to the basilar artery BA orposterior cerebral arteries PCA via a cut down incision in the vertebralartery or a percutaneous puncture of the vertebral artery for access toocclusions in the posterior cerebral vasculature such as the posteriorcerebral artery or basilar artery. For entry into the common carotidartery, the arterial access device can be inserted into an openingdirectly in the common carotid artery, the opening being positionedabove the patient's clavicle and below a bifurcation location where thepatient's common carotid artery bifurcates into an internal carotidartery and external carotid artery. For example, the opening may belocated at a distance of around 3 cm to 7 cm below a bifurcationlocation where the patient's common carotid artery bifurcates into aninternal carotid artery and external carotid artery.

The system may also include an intermediate guide catheter. FIG. 3 showsa guide catheter 2105 that is inserted through an arterial access sheath2010 via the access device proximal hemostasis valve 2012. The guidecatheter 2105 includes a proximal adaptor having a proximal port 2015with a hemostasis valve to allow introduction of devices whilepreventing or minimizing blood loss during the procedure. The guidecatheter 2105 may also include an occlusion balloon 2020 at the distalregion.

The systems shown in FIGS. 1, 2 and 3 may also include one or morecatheters 2030 to provide distal access for additional devices,localized fluid or contrast delivery, or localized aspiration at alocation distal of the distal-most end of the arterial access device2010. A single catheter may be adequate for accessing and treating theocclusion or occlusions. A second, smaller diameter catheter may beinserted through the first catheter or exchanged for the first catheterif more distal access is desired and not possible with the initialcatheter. In an embodiment, the catheter 2030 is sized and shaped orotherwise configured to be inserted into the internal lumen of thearterial access device 2010 via the port 2015. The catheter 2030 may usea previously placed guide wire, microcatheter, or other device acting asa guide rail and support mechanism to facilitate placement near the siteof the occlusion. The catheter may also utilize a dilator element tofacilitate placement through the vasculature over a guidewire. Once thecatheter is positioned at or near the target site, the dilator may beremoved. The catheter 2030 may then be used to apply aspiration to theocclusion. The catheter 2030 or dilator may also be used to deliveradditional catheters and/or interventional devices to the site of theocclusion.

The disclosed methods and devices also include devices to protect thecerebral penumbra during the procedure to minimize injury to the brain.A distal perfusion device may be used during the procedure to provideperfusion to the brain beyond the site of the occlusion, therebyreducing the injury to the brain from lack of blood. These perfusiondevices may also provide a way to reduce the forward blood pressure onthe occlusion in the vessel and thus assist in removing the occlusion,for example using either aspiration, a mechanical element, or both.

The system may also include accessory devices such as guidewires andmicrocatheters, and stroke treatment devices such as stent retrievers,snares, or other thrombectomy devices, which have been optimallyconfigured for reaching a target cerebral or intracranial treatment sitevia a transcarotid access site. For example, the system may include athrombectomy device 4100. In addition, the disclosed methods and devicesprovide for securely closing the access site to the cerebral arteries toavoid the potentially devastating consequences of a transcarotidhematoma. The present disclosure provides additional methods anddevices.

Exemplary Embodiments of Arterial Access Devices

Described herein are arterial access devices, also referred to herein asarterial access sheaths or sheath systems. U.S. Patent Publication No.2014/02196769; and U.S. Provisional Application Ser. No. 62/075,169entitled “METHODS AND DEVICES FOR TRANSCAROTID ACCESS” and filed Nov. 4,2014; and U.S. patent application Ser. No. 14/537,316 entitled “METHODSAND DEVICES FOR TRANSCAROTID ACCESS” and filed Nov. 10, 2014 which areeach incorporated by reference herein, also describe arterial accessdevices of consideration herein.

As described above, FIGS. 1, 2 and 3 illustrates embodiments of anarterial access sheath 2010 that is configured to be directly insertedinto the common carotid artery (CCA) without use of a separateintroducer sheath. The sheath 2010 can be inserted over a guidewire ofan initial access system. FIG. 4 shows an embodiment of a transcarotidinitial access system 100 or a micro access kit for establishing initialaccess to a carotid artery for the purpose of enabling introduction of aguide wire into the carotid artery. The access to the carotid artery canoccur at an access site located in the neck of a patient such as in theregion of the patient's carotid artery. The devices of the transcarotidinitial access system 100 are particularly suited for directly accessingthe carotid artery through the wall of the common carotid artery. Thetranscarotid initial access system 100 can include an access needle 120,access guidewire 140, and micropuncture cannula 160. The micropuncturecannula 160 can include a cannula body 162 and an inner dilator 168slidably positioned within a lumen of the body 162. The inner dilator168 can have a tapered tip and provide a smooth transition between thecannula and the access guidewire 140. The micropuncture cannula 160 canalso include a radiopaque marker 164 near a distal tip of the cannula160 to help the user visualize the tip location under fluoroscopy. Theaccess guidewire 140 can include guide wire markings 143 to help theuser determine where the tip of the guide wire 140 is with respect tothe cannula 160. The access needle 120, access guidewire 140, andmicropuncture cannula 160 are all adapted to be introduced via a carotidpuncture into the carotid artery. The carotid puncture may beaccomplished, for example, percutaneously or via a surgical cut down.Embodiments of the initial access system 100 may be adapted towards oneor the other method of puncture.

In an alternate embodiment, the arterial access device 2010 may beconfigured for access to the common carotid artery CCA from a femoralartery access site, also without the use of a separate introducersheath. As above, the access device includes a proximal adaptor with aproximal port 2015 with a hemostasis valve and a connection to a flowline 2025 (or shunt) which may be connected to means for passive oractive reverse flow. The flow line 2025 has an internal lumen thatcommunicates with an internal lumen of the arterial access device 2010for shunting blood from the arterial access device. In both transfemoraland transcarotid embodiments, the connection to the flow line isoptimized for aspiration of thrombus with flow lumens at least as largeas the ID of the arterial access device 2010.

Upon establishment of access to the carotid artery using the initialaccess system 100, an arterial access sheath of a sheath system such asthose described herein may be inserted into the carotid artery at theaccess site. FIG. 5 shows an embodiment of a transcarotid access sheathsystem 200 of devices for inserting an access sheath into the carotidartery, for example, over a sheath guidewire of an initial accesssystem. When inserted into the carotid artery, the access sheath system200 allows for the introduction of at least one interventional deviceinto the carotid artery via a lumen of the access sheath for the purposeof performing an interventional procedure on a region of thevasculature. The transcarotid access sheath system 200 can include anaccess sheath 220, a sheath dilator 260, and a sheath guidewire 300. Theaccess sheath 220, sheath dilator 260 and sheath guidewire 300 are alladapted to be introduced via a carotid puncture into the carotid artery.The carotid puncture may be accomplished percutaneously or via asurgical cut down. Embodiments of the access sheath system 200 may beadapted towards one or the other method of puncture.

In an embodiment, some or all of the components of transcarotid initialaccess system 100 and the transcarotid access sheath system 200 may becombined into one transcarotid access system kit such as by combiningthe components into a single, package, container or a collection ofcontainers that are bundled together.

The arterial access sheath systems described herein can include a distalportion configured to be inserted in the vessel and a proximal portionconfigured to extend outward from the access site when the distalportion of the arterial access sheath is positioned in the arterialpathway. For example with reference to FIG. 5, the arterial accesssheath 220 has an elongated sheath body 222 sized and shaped such thatat least a portion of the sheath body 222 is insertable into the arteryduring a procedure while the proximal portion remains outside the body.The elongated sheath body 222 is the portion of the arterial accesssheath 220 that is sized and shaped to be inserted into the artery andwherein at least a portion of the elongated sheath body is actuallyinserted into the artery during a procedure. A proximal adaptor 224 canbe positioned near a proximal end of an elongated sheath body 222 (seealso, e.g. port 2015 of FIG. 1). The proximal adaptor 224 is configuredto remain outside the body when at least a portion of the sheath body222 is inserted into the artery. The proximal adaptor 224 can have ahemostasis valve 226 that communicates with the internal lumen of thesheath body 222. The hemostasis valve 226 that communicates with theinternal lumen of the sheath body 222 allow for the introduction ofdevices therein while preventing or minimizing blood loss via theinternal lumen during the procedure. The hemostasis valve 226 can be astatic seal-type passive valve, or an adjustable-opening valve such as aTuohy-Borst valve 227 or rotating hemostasis valve (RHV) (see FIG. 6).The hemostasis valve may be integral to the proximal adaptor 224, or theaccess sheath 220 may terminate on the proximal end in a female Lueradaptor to which a separate hemostasis valve component, such as apassive seal valve, a Tuohy-Borst valve or rotating hemostasis valve,may be attached. Further, one or more features can be positioned nearthe proximal end of the access sheath 220 to aid in securement of thesheath during the procedure. For example, the access sheath 220 may havea suture eyelet 234 or one or more ribs 236 molded into or otherwiseattached to the adaptor 224, which would allow the operator to suturetie the sheath hub to the patient.

In an embodiment, the sheath body 222 can have an inner diameter ofabout 0.087″ and an outer diameter of about 0.104″, corresponding to a 6French sheath size. In another embodiment, the sheath body 222 has aninner diameter of about 0.113″ and an outer diameter of about 0.136″,corresponding to an 8 French sheath size. In an embodiment, the sheathlength is between 10 and 12 cm. In another embodiment, the sheath lengthis between 15 and 30 cm. The diameter and length most suitable to aparticular embodiment is dependent on the location of the target siteand nature of the devices and flow requirements through the lumen of theaccess device 200.

In some instances it is desirable to move the proximal port and/or thehemostasis valve away from the distal tip of the arterial access sheatheffectively elongating or lengthening the proximal portion (also calleda proximal extension herein) that is outside the body while maintainingthe length of the insertable distal portion. This allows the user toinsert devices into the proximal port of the proximal extension and fromthere into the lumen of the arterial access device from a point furtheraway from the target site and from the image intensifier used to imagethe target site fluoroscopically thereby minimizing radiation exposureof the user's hands and also his or her entire body. The proximalextension can be configured such that the length between the proximalport and the arterial access site is between about 30 cm and about 50cm. The proximal extension can be removable from the arterial accessdevice. An example of a proximal extension design is described inco-pending U.S. Application Publication No. 2010/0042118, filed Aug. 12,2009, which is incorporated herein by reference. U.S. Pat. No.8,574,245, U.S. Application Publication No. 2010/0217276, and U.S.Application Publication No. 2011/0087147, which each are alsoincorporated by reference herein.

FIG. 10 also illustrates an embodiment of an arterial access sheath 220having a proximal extension portion 805. The proximal extension 805 canhave a length suitable to meaningfully reduce the radiation exposure tothe user during a transcarotid access procedure. For example, theproximal extension 805 is between about 10 cm and about 25 cm, orbetween about 15 cm and about 20 cm. Alternately, the proximal extension805 has a length configured to provide a distance of between about 30 cmand about 60 cm between the hemostasis valve 226 and the distal tip ofthe sheath body, depending on the insertable length of the accesssheath. A connector structure 815 can connect the elongated sheath body222 to the proximal extension 805. In this embodiment, the connectorstructure 815 may include a suture eyelet 820 and/or ribs 825 to assistin securing the access sheath 220 to the patient. In an embodiment, thehemostasis valve 226 is a static seal-type passive valve. In analternate embodiment the hemostasis valve 226 is an adjustable-openingvalve such as a Tuohy-Borst valve 227 or rotating hemostasis valve(RHV). Alternately, the proximal extension 805 may terminate on theproximal end in a female Luer adaptor to which a separate hemostasisvalve component may be attached, either a passive seal valve, aTuohy-Borst valve or rotating hemostasis valve (RHV).

The proximal extension and/or proximal adaptor 224 can have a largerinner and outer diameter than the sheath body 222 or the portion of theaccess sheath configured to be inserted arterially. In instances wherethe outer diameter of the catheter being inserted into the sheath isclose to the inner diameter of the sheath body, the annular space of thelumen that is available for flow is restrictive. Minimizing the sheathbody length is thus advantageous to minimize this resistance to flow,such as during flushing of the sheath with saline or contrast solution,or during aspiration or reverse flow out of the sheath. Again withrespect to FIG. 10, the sheath body 222 can have an inner diameter ofabout 0.087″ and an outer diameter of about 0.104″, corresponding to a 6French sheath size, and the proximal extension has an inner diameter ofabout 0.100″ to about 0.125″ and an outer diameter of about 0.150″ toabout 0.175″. In another embodiment, the sheath body 222 has an innerdiameter of about 0.113″ and an outer diameter of about 0.136″,corresponding to an 8 French sheath size, and the proximal extension hasan inner diameter of about 0.125″ and an outer diameter of about 0.175″.In yet another embodiment, the sheath body 222 is stepped with a smallerdiameter distal section 605 to further reduce flow restriction, as inFIG. 8.

The proximal extension 905 on the arterial access sheath 220 may beremovable. Typically, vessel closure devices requires an arterial accesssheath with a maximum distance of about 15 cm between distal tip of thesheath body to the proximal aspect of the hemostasis valve, with sheathbody of about 11 cm and the remaining 4 cm comprising the length of theproximal hemostasis valve; thus if the access sheath has a distance ofgreater than 15 cm it is desirable to remove the proximal extension atthe end of the procedure. Again with respect to FIG. 10, the proximalextension 805 can be removable in such a way that after removal,hemostasis is maintained. For example, a hemostasis valve is built intothe connector 815 between the sheath body 222 and the proximal extension805. The hemostasis valve can be opened when the proximal extension 805is attached to allow fluid communication and insertion of devices, butprevents blood flowing out of the sheath 220 when the proximal extension805 is removed. After the procedure is completed, the proximal extension805 can be removed, reducing the distance between the proximal aspect ofthe hemostasis valve and sheath tip from greater than 15 cm to equal orless than 15 cm and thus allowing a vessel closure device to be usedwith the access sheath 220 to close the access site.

The arterial access sheath systems described herein are suitable orparticularly optimized to provide transcarotid arterial access forreaching various treatment sites from that access site. The workinglength of the arterial access sheath or sheath/guide catheter systemdescribed herein can be considerably shorter than that of long sheathsor sheath guide systems placed, for example, from an access location inthe femoral artery. The distance from the femoral artery to the commoncarotid artery (CCA) is about 60-80 cm moving through the artery. Thus,arterial access devices using a CCA access site may be shorter by atleast this amount. Femoral arterial access used to access or deploy adevice in the cervical ICA (e.g. the Balloon Guide, Concentric, Inc.)are typically 80-95 cm in length. Femoral arterial access used to accessor deploy a device in the petrous ICA (e.g. the Neuron 6F Guide,Penumbra, Inc.) are typically 95-105 cm in length. The shorter lengthsof access devices disclosed herein reduces the resistance to flowthrough the lumen of these devices and increases the rate at whichaspiration and/or reverse flow may occur. For example, in an embodiment,the elongated sheath body 222 has a length in the range of about 10 cmto about 12 cm. For access to a same target site from a femoral accesssite, the access sheaths are typically between 80 cm and 110 cm, or aguide catheter is inserted through an arterial access sheath andadvanced to the target site. However, a guide catheter through an accesssheath takes up luminal area and thus restricts the size of devices thatmay be introduced to the target site. Thus, an access sheath that allowsinterventional devices to reach a target site without a guide catheterhas advantages over an access sheath that requires use of a guidecatheter to allow interventional devices to the target site.

It should be appreciated that the length and inner diameter of thearterial access sheaths described herein can vary depending on thedesired target position of the sheath distal tip. In one embodiment, anaccess sheath is adapted to be inserted into the common carotid artery(CCA) with the distal tip positioned in the CCA or proximal ICA. In thisembodiment, the sheath can have an elongated sheath body 222 having alength in the range of from about 7 cm to about 15 cm, usually beingfrom about 10 cm to about 12 cm, The length considered herein can be thelength extending from the proximal adapter 224 to a distal tip of theelongated sheath body 222. For a sheath adapted to be inserted via thecommon carotid artery (CCA) to a more distal site in the mid or distalinternal carotid artery the length of the elongated sheath body 222 canbe in the range from about 10 cm to about 30 cm, usually being fromabout 15 cm to about 25 cm. In another example embodiment, the arterialaccess device has a length of about 10 cm to about 40 cm. In anotherembodiment, the length of the arterial access device is about 10.5 cmand a separate guide catheter inserted through the access device has alength of about 32 cm.

In some procedures it may be desirable to incorporate features on thearterial access sheath in order to minimize flow resistance through theinsertable portion of the access sheath, for example, as described inU.S. Pat. No. 7,998,104 to Chang and U.S. Pat. No. 8,157,760 to Criado,which are both incorporated by reference herein. For example, FIG. 8shows such an embodiment of the sheath body 222 having a stepped ortapered configuration such that the sheath body 222 has a reduceddiameter distal region 705 (with the reduced diameter being relative tothe remainder of the sheath). The distal region 705 of the steppedsheath can be sized for insertion into the carotid artery. The innerdiameter of the distal region 705 can be in the range from 0.065 inch to0.115 inch with the remaining proximal region of the sheath havinglarger outside and luminal diameters. The inner diameter of theremaining proximal region can typically be in the range from 0.110 inchto 0.135 inch. The larger luminal diameter of the remainder of thesheath body 222 minimizes the overall flow resistance through the sheath220. In an embodiment, the reduced-diameter distal region 705 has alength of approximately 2 cm to 4 cm. The relatively short length of thereduced-diameter distal region 705 permits this section to be positionedin the common carotid artery CCA via a transcarotid approach withreduced risk that the distal end of the sheath body 222 will contact thebifurcation. In an alternate embodiment, the sheath body is configuredto have an insertable portion that is designed to reach as far as thedistal ICA. In this embodiment, the reduced-diameter distal section 605has a length of approximately 10 cm to 15 cm, with a total sheath bodylength of 15-25 cm. The reduced diameter section permits a reduction insize of the arteriotomy for introducing the sheath into the artery whilehaving a minimal impact in the level of flow resistance. Further, thereduced distal diameter region 705 may be more flexible and thus moreconformal to the lumen of the vessel.

In some instances it may be desirable to connect the access sheath to aflow line, for example for the purposes of passive or active aspirationto reduce the risk of distal emboli during the procedure. In anembodiment shown in FIG. 11, the arterial access sheath 220 has a lowresistance (large bore) flow line or shunt connected to the accesssheath. The low resistance flow line 905 can be connected to an internallumen of the sheath body 222 via a Y-arm 915 of the connector 815. Theflow line 905 may be connected to a lower pressure return site such as avenous return site or a reservoir. The flow line 905 may also beconnected to an aspiration source such as a pump or a syringe. As shownin FIG. 11, the flow line 905 can be located distal of the locationwhere devices enter the proximal port 226 of the arterial access sheath220. In an alternate embodiment, the flow line 905 is attached to theY-arm of a separately attached Tuohy Borst valve.

The flow line can be connected to an element configured for passiveand/or active reverse flow such that blood from the arterial accesssheath can be shunted. Connecting the flow line to a lower pressuresystem, such as a central vein or a reservoir, is an example of passivereverse flow. The reservoir may be positioned on a table near thepatient, for a pressure of approximately zero, or positioned below thetable to create negative pressure. Examples of devices for activereverse flow are a syringe or other manual aspiration device, or anaspiration pump. The passive or active reverse flow device may beactuated via a stopcock or other flow control switch during criticalperiods of the procedure, for example when thrombus is being pulled outof the occluded area, into the sheath, and out of the patient. In anembodiment, the flow control switch is integral to the arterial accessdevice. In an alternate embodiment, the flow control switch is aseparate component. Because it may be desirable to remove all thrombusfrom the device with minimal to no chance of material being caught inirregular surfaces or connection surfaces, an embodiment of the accessdevice is constructed such that there is a continuous inner surface withno ledges or crevices at the junction(s) between the lumen of the sheathbody, the Y-arm, the flow control switch, the flow line, and theaspiration source.

In some instances it is desirable for the sheath body to also be able toocclude the artery in which it is positioned, for examples in proceduresthat may create distal emboli. In these cases, occluding the arterystops antegrade blood flow in the artery and thereby reduces the risk ofdistal emboli that may lead to neurologic symptoms such as TIA orstroke. The arterial access device 2010 of FIG. 1 or FIG. 2 may have anocclusion balloon 2020 configured to occlude the artery when inflated.In turn, the arterial access device 2010 may also include a lumen forballoon inflation. This lumen fluidly connects the balloon, for example,to a second Y-arm on the proximal adaptor. This Y-arm is attached to atubing 2028 which terminates in a one-way stopcock 2029. An inflationdevice such as a syringe may be attached to the stopcock 2029 to inflatethe balloon when vascular occlusion is desired. FIG. 9 shows anembodiment of an arterial access sheath 220 with an inflatable balloon705 on a distal region that is inflated via an inflation line 710 thatconnects an internal inflation lumen in the sheath body 222 to astopcock 229, which in turn may be connected to an inflation device. Inthis embodiment, there is also a Y-arm 715 that may be connected to apassive or active aspiration source to further reduce the risk of distalemboli.

In some configurations, an intermediate guide catheter may be insertedthrough the arterial access device to provide additional cathetersupport and potentially distal occlusion. FIG. 3 shows a system with aguide catheter 2105 inserted into the CCA through the proximalhemostasis valve 2012 of the arterial access device 2010. The guidecatheter 2105 includes a proximal adaptor having a proximal port 2015with a hemostasis valve to allow introduction of devices whilepreventing or minimizing blood loss during the procedure. The guidecatheter 2105 may also include an occlusion balloon 2020 and a lumen forballoon inflation that is attached to a Y-arm in the proximal adaptor,which in turn is connected to a tubing 2128. The tubing 2128 terminatesin a one-way stopcock 2129 for connection to a balloon inflation device.The guide catheter 2105 may include a second Y-arm 2107 thatcommunicates with a flow line 2125. Introduction through the separatesheath 2110 allows removal of the guide catheter 2105 for flushingoutside the patient and reinserting, or for exchanging the guidecatheter 2105 with another guide catheter without removing theintroducer sheath 2110, thus maintaining access to the artery via thetranscarotid incision. This configuration also allows repositioning ofthe occlusion balloon 2020 during the procedure without disturbing thearterial insertion site. The embodiment of FIG. 11 also allows removalof the arterial access device 2105 and then insertion of a vesselclosure device through the introducer sheath 2110 at the conclusion ofthe procedure.

In yet another embodiment, as shown in FIG. 12, the arterial accessdevice is a device 2010 with two occlusion balloons 2405 and 2410 and aside opening 2415 positioned between the two balloons. The distalocclusion balloon 2410 is located at or near the distal end of thearterial access device 2010, and the proximal occlusion balloon 2405 islocated between the distal end and the proximal end of the workingportion of the arterial access device. The distal occlusion balloon 2410is sized and shaped to be placed in the external carotid artery ECA andthe proximal occlusion balloon 2405 is sized and shaped to be placed inthe common carotid artery CCA. Such a dual balloon configuration stopsflow into the internal carotid artery ICA from both the CCA and the ECA,which has an effect functionally the same as an occlusion balloonpositioned in the ICA without inserting a device into the ICA. This maybe advantageous if the ICA were diseased, whereby access may causeemboli to dislodge and create embolic complications, or the access tothe ICA were severely tortuous and difficult to achieve, or both. Theside opening 2415 in the working section of the arterial access device2105 permits a device 2416 to be introduced via the arterial accessdevice 2010 and inserted into the ICA via the side opening 2415 whileflow is stopped or reversed, to reduce or eliminate the risk of distalemboli. This device 2416 may then be advanced to the location of thecerebral artery occlusion to treat the occlusion.

In yet another embodiment, as shown in FIG. 13 the arterial accessdevice is a multi-part (such as two-part) telescoping system. The accesssheath 2010 b and/or the distal extension 2010 c can be formed of two ormore concentric, tubular sections that telescopically slide relative toone another to increase and/or decrease the entire collective length ofthe movably attached tubular sections. The first part is an accesssheath 2010 b that is configured to be inserted directly into the CCA.The second part is a distal extension 2010 c which is inserted throughthe proximal end of the introducer sheath 2010 b and which extends thereach of the sheath into the ICA. The distal end of the sheath 2010 band the proximal end of the extension 2010 c form a lap junction 2113when the extension is fully inserted, such that there is a continuouslumen through the two devices. The lap junction may be variable length,such that there is some variability in the length of the combinedtelescoping system 2105 b. The distal extension 2010 c can include atether which allows placement and retrieval of the distal extension 2010c through the sheath 2010 b. In an embodiment, the distal extension 2010c includes an occlusion balloon 2815. In this embodiment the tether 2835include a lumen for inflation of the balloon. This tether can beconnected on the proximal end to a balloon inflation device. Thisconfiguration provides the advantages of sheath plus guide cathetersystem shown in FIG. 3, without compromising the luminal area.

The arterial access devices described herein may be configured so thatit can be passed through or navigate bends in the artery withoutkinking. For example, when the access sheath is being introduced throughthe transcarotid approach, above the clavicle but below the carotidbifurcation, it is desirable that the elongated sheath body 222 beflexible while retaining hoop strength to resist kinking or buckling.This can be especially important in procedures that have limited amountof sheath insertion into the artery and/or where there is a steep angleof insertion as with a transcarotid access in a patient with a deepcarotid artery and/or with a short neck. In these instances, there is atendency for the sheath body tip to be directed towards the back wall ofthe artery due to the stiffness of the sheath. This causes a risk ofinjury from insertion of the sheath body itself, or from devices beinginserted through the sheath into the arteries, such as guide wires.Alternately, the distal region of the sheath body may be placed in adistal carotid artery which includes one or more bends, such as thepetrous ICA. Thus, it is desirable to construct the sheath body 222 suchthat it can be flexed when inserted in the artery, while not kinking. Inan embodiment, the arterial access device can be and is passed throughbends of less than or equal to 45 degrees wherein the bends are locatedwithin 5 cm, 10 cm, or 15 cm of the arteriotomy measured through theartery.

The working portion of the arterial access sheath, such as the sheathbody which enters the artery, can be constructed in two or more layers.An inner liner can be constructed from a low friction polymer such asPTFE (polytetrafluoroethylene) or FEP (fluorinated ethylene propylene)to provide a smooth surface for the advancement of devices through theinner lumen. An outer jacket material can provide mechanical integrityto the inner liner and may be constructed from materials such as Pebax,thermoplastic polyurethane, polyethylene, nylon, or the like. A thirdlayer can be incorporated that can provide reinforcement between theinner liner and the outer jacket. The reinforcement layer can preventflattening or kinking of the inner lumen of the sheath body as thedevice navigates through bends in the vasculature. The reinforcementlayer can also provide for unimpeded lumens for device access as well asaspiration or reverse flow. In an embodiment, the sheath body 222 iscircumferentially reinforced. The reinforcement layer can be made frommetal such as stainless steel, Nitinol, Nitinol braid, helical ribbon,helical wire, cut stainless steel, or the like, or stiff polymer such asPEEK. The reinforcement layer can be a structure such as a coil orbraid, or tubing that has been laser-cut or machine-cut so as to beflexible. In another embodiment, the reinforcement layer can be a cuthypotube such as a Nitinol hypotube or cut rigid polymer, or the like.

The arterial access sheaths described herein can have a sheath body thatvaries in flexibility over its length. As described above, a distal-mostportion of the arterial access device may be configured to be moreflexible than a proximal section of the device. In one embodiment, thereis a distal-most section of sheath body 222 that is more flexible thanthe remainder of the sheath body. The distal section may be at least 10%of the length of the working portion of the catheter wherein the workingportion is the portion that is configured to be inserted into an artery.In other embodiments, the distal section is at least 20% or at least 30%of the length of the working portion of the catheter. The variability inflexibility may be achieved in various ways. For example, the outerjacket may change in durometer and/or material at various sections. Alower durometer outer jacket material can be used in a distal section ofthe sheath compared to other sections of the sheath. Alternately, thewall thickness of the jacket material may be reduced, and/or the densityof the reinforcement layer may be varied to increase the flexibility.For example, the pitch of the coil or braid may be stretched out, or thecut pattern in the tubing may be varied to be more flexible.Alternately, the reinforcement structure or the materials may changeover the length of the sheath body. For example, the flexural stiffnessof the distal-most section can be one third to one tenth the flexuralstiffness of the remainder of the sheath body 222. In an embodiment, thedistal-most section has a flexural stiffness (E*I) in the range 50 to300 N-mm² and the remaining portion of the sheath body 222 has aflexural stiffness in the range 500 to 1500 N-mm², where E is theelastic modulus and I is the area moment of inertia of the device. For asheath configured for a CCA access site, the flexible, distal mostsection comprises a significant portion of the sheath body 222 which maybe expressed as a ratio. In an embodiment, the ratio of length of theflexible, distal-most section to the overall length of the sheath body222 is at least one tenth and at most one half the length of the entiresheath body 222.

In some instances, the arterial access sheath is configured to access acarotid artery bifurcation or proximal internal carotid artery ICA froma CCA access site. As best shown in FIG. 5, the sheath body 222 can havea distal-most section 223 which is about 3 cm to about 4 cm and theoverall sheath body 222 is about 10 cm to about 12 cm. In thisembodiment, the ratio of length of the flexible, distal-most section tothe overall length of the sheath body 222 is about one forth to one halfthe overall length of the sheath body 222. In another embodiment, thereis a transition section 225 between the distal-most flexible section andthe proximal section 231, with one or more sections of varyingflexibilities between the distal-most section and the remainder of thesheath body. In this embodiment, the distal-most section is about 2 cmto about 4 cm, the transition section is about 1 cm to about 2 cm andthe overall sheath body 222 is about 10 cm to about 12 cm, or expressedas a ratio, the distal-most flexible section and the transition sectioncollectively form at least one fourth and at most one half the entirelength of the sheath body.

In some instances, the sheath body 222 of the arterial access sheath isconfigured to be inserted more distally into the internal carotid arteryrelative to the arterial access location, and possibly into theintracranial section of the internal carotid artery. For example, adistal-most section 223 of the elongated sheath body 222 is about 2.5 cmto about 5 cm and the overall sheath body 222 is about 15 cm to about 30cm in length. In this embodiment, the ratio of length of the flexible,distal-most section to the overall length of the sheath body is onetenth to one quarter of the entire sheath body 222. In anotherembodiment, there is a transition section 225 between the distal-mostflexible section and the proximal section 231, in which the distal-mostsection is about 2.5 cm to about 5 cm, the transition section is about 2cm to about 10 cm and the overall sheath body 222 is about 15 cm toabout 30 cm. In this embodiment, the distal-most flexible section andthe transition section collectively form at least one sixth and at mostone half the entire length of the sheath body.

In some instances it is desirable to keep the sheath tip as small aspossible during sheath insertion to minimize the diameter of thearterial puncture, but to expand the opening of the sheath after it hasbeen inserted into the vessel. At least one purpose of this feature isto minimize the effect or creation of distal emboli during pull back ofan aspiration catheter or other thrombectomy device into the sheath.During a thrombectomy procedure, the thrombus may be “pulled back” intoa distal opening of the sheath on a device that has captured thethrombus. If the distal tip of the sheath is enlarged relative to itsinitial size, the chance of pieces of the thrombus breaking off andcausing emboli is minimized because the larger size of the sheath tip ismore likely to accommodate the emboli being drawn into it without beingsplit into multiple pieces. This creates a better clinical outcome forthe patient. In an embodiment of the arterial access device, thearterial access device is made of a material and/or constructed suchthat a tip of the sheath body of the access device can be expanded to alarger diameter once inserted into the artery and positioned in itsdesired location. In an embodiment, the distal region of the sheath hasan ID of about 0.087″ can be enlarged to a diameter of about 0.100″ to0.120″ although the size may vary.

Examples of expanding distal tip constructions include covered braidedtips that can be shortened to expand. Another example of an expandingdistal tip construction is an umbrella or similar construction that canopen up with mechanical actuation or elastic spring force whenunconstrained. Other mechanisms of expandable diameter tubes are wellknown in the art. One particular embodiment is a sheath made of materialthat is deformable when expanded using a high pressure balloon.

FIG. 15 shows an example of an arterial access device comprised of asheath 4305 that has an expandable distal tip. As in other embodiments,the sheath 4305 has an internal lumen sized and shaped to receive adilator 4310, which is shown protruding out of the distal end of thesheath 4305. The proximal region of the sheath 4305 may be equipped withany of a variety of Y-arms, valves, actuators, etc. FIG. 16 shows anenlarged view of the distal region of the sheath 4305 with the dilator4310 protruding outward. In the view of FIG. 16, the distal region ofthe sheath is unexpanded. The dilator 4310 is equipped with anexpandable balloon 4505 that may be aligned at a desired location alongthe sheath 4305 by sliding the dilator 4310 forward or backward relativeto the sheath 4305. The dilator may have an inflation lumen andinflation device for inflating the balloon 4505. When the dilator 4310is inserted into the arterial access device sheath 4305, the balloon4405 can be aligned at a desired location of the sheath 4305. When theballoon 4505 is inflated, a precise length or region of the sheath 4305is expanded to a precise diameter as a result of the balloon 4505expanding inside the sheath. Once the sheath tip is in its desiredlocation, the balloon is inflated to a pressure that would expand thesheath, as shown in FIG. 17 where a distal region R of the sheath bodyhas been expanded. FIG. 18 shows the sheath 4305 with the region Rexpanded as a result of the balloon 4505 being expanded while inside thesheath 4305. In an embodiment, the distal region R is plasticallyexpanded. The sheath body is constructed such that it could stretch tothis larger diameter without tearing or breaking. The balloon materialmay be a non-compliant or semi-compliant material similar or identicalto those used in angioplasty balloons, such as nylon. These materialsmay be inflated to a very high pressure without expanding past theengineered diameter. In a variation, the balloon inflation member isseparate from the dilator or on a second dilator, and exchanged for theinitial dilator used for sheath insertion, once the sheath is in itsdesired location. The expanding tip design may be used in place of or inconjunction with an occluding balloon on the sheath to minimize the riskof distal emboli.

The arterial access devices described herein can also be adapted toreduce, minimize or eliminate a risk of injury to the artery caused bythe distal-most sheath tip facing and contacting the posterior arterialwall. In some embodiments, the sheath has a structure configured tocenter the sheath body tip in the lumen of the artery such that thelongitudinal axis of the distal region of the sheath body is generallyparallel with the longitudinal or center axis of the lumen of thevessel. The sheath alignment feature 508 can be one or more mechanicalstructures on the sheath body 222 that can be actuated to extend outwardfrom the sheath tip (see FIG. 7). The sheath alignment feature 508 canbe an inflatable, enlargeable, extendible bumper, blister, or balloon,located on an outer wall of the arterial access sheath 220. The sheathalignment feature 508 may be increased in size to exert a force on theinner arterial wall to contact and push the elongated body 222 of thearterial access sheath away from the arterial wall. In an embodiment,the sheath body 222 is configured to be inserted into the artery suchthat a particular edge of the arterial access is against the posteriorwall of the artery. In this embodiment, the sheath alignment feature 508can extend outward from one direction relative to the longitudinal axisof the sheath body 222 to lift or push the sheath tip away from theposterior arterial wall. The alignment feature 508 can be positioned onone side of the sheath body 222 as shown in FIG. 7 or on more than oneside of the sheath body 222.

In another embodiment, at least a portion of the sheath body 222 ispre-shaped so that after sheath insertion the tip is more aligned with along axis of the vessel within which it is inserted, even at a steepsheath insertion angle. In this embodiment, the sheath body 222 isgenerally straight when the dilator 260 is assembled with the sheath 220during sheath insertion over the sheath guide wire 300, but once thedilator 260 and guidewire 300 are removed, the distal-most section ofthe sheath body 222 can assume a curved or angled shape. In anembodiment, the sheath body 222 is shaped such that the distal-most 0.5cm to 1 cm section is angled from 10 to 30 degrees, as measured from themain axis of the sheath body 220, with a radius of curvature about 0.5″.To retain the curved or angled shape of the sheath body 220 after havingbeen straightened during insertion, the sheath 220 may be heat set inthe angled or curved shape during manufacture. Alternately, areinforcement structure may be constructed out of nitinol andheat-shaped into the curved or angled shape during manufacture.Alternately, an additional spring element may be added to the sheathbody 220, for example a strip of spring steel or nitinol, with thecorrect shape, added to the reinforcement layer of the sheath 220.

In some procedures, it may be desirable to limit the amount of sheathbody 222 insertion into the artery, for example in procedures where thetarget area is very close to the arterial access site. In a stentprocedure of the carotid artery bifurcation, for example, the sheath tipshould be positioned proximal of the treatment site (relative to theaccess location) so that it does not interfere with stent deployment orenter the diseased area and possibly cause emboli to get knocked loose.In an embodiment of arterial sheath 220 shown in FIGS. 14A and 14B, asheath stopper 1005 is slideably connected or mounted over the outsideof the distal portion of the sheath body. The sheath stopper 1005 isshorter than the distal portion of the sheath, effectively shorteningthe insertable portion of the sheath body 222 by creating a positivestop at a certain length along the sheath body 222. The sheath stopper1005 may be a tube that slidably fits over the sheath body 222 with alength that, when positioned on the sheath body 222, leaves a distalportion of the sheath body exposed. This length can be in the rangeabout 2 cm to about 4 cm. More particularly, the length is about 2.5 cm.The distal end of the sheath stopper 1005 may be angled and orientedsuch that the angle sits flush with the vessel and serves as a stopagainst the arterial wall when the sheath is inserted into the arterywhen the vessel is inserted into the artery, as shown in FIG. 14A.Alternately, the distal end of the sheath stopper may be formed into anangled flange 1015 that contacts the arterial wall, as shown in FIG.14B. The flange 1015 is rounded or has an atraumatic shape to create amore positive and atraumatic stop against the arterial wall. The sheathstopper 1005 may be permanently secured to the arterial sheath, forexample the proximal end of the sheath stopper may be adhered toconnector 815 of the arterial access sheath. Alternately, the sheathstopper 1005 may be removable from the arterial access sheath 220 by theuser so it can be optionally utilized in a procedure. In this instance,the sheath stopper 1005 may have a locking feature on the proximalportion that engages with a corresponding locking features on theconnector 815, for example slots or recesses on the proximal sheathstopper engaging protrusions on the connector. Other locking featuresmay also be utilized.

In situations where the insertion of the sheath body is limited tobetween about 2 cm and about 3 cm, and particularly when the sheath body222 is inserted at a steep angle, the sheath 220 may conform to abayonet shape when secured to the patient. For example, the bayonetshape may comprise a first portion that extends along a first axis and asecond portion that extends along a second axis that is axially offsetfrom the first axis and/or non-parallel to the first axis. Thespringiness of the sheath body 222 causes this shape to exert a force onthe vessel at the site of insertion and increase the tendency of thesheath 220 to come out of the vessel if not properly secured. To reducethe stress on the vessel, the sheath stopper may be pre-shaped into acurved or bayonet shape so that the stress of the sheath body whencurved is imparted onto the sheath stopper rather than on the vessel.The sheath stopper 1005 may be made from springy but bendable materialor include a spring element such as a stainless steel or nitinol wire orstrip, so that when the dilator 260 is inserted into the sheath 220 andsheath stopper 1005, the sheath 220 is relatively straight, but when thedilator 260 is removed the sheath stopper 1005 assumes the pre-curvedshape to reduce the force the sheath 220 imparts on the vessel wall.Alternately, the sheath stopper 1005 may be made of malleable materialor include a malleable element such as a bendable metal wire or strip,so that it can be shaped after the sheath 220 is inserted into a desiredcurvature, again to reduce the stress the sheath 220 imparts on thevessel wall.

The access sheaths described herein can have a lubricious or hydrophiliccoating to reduce friction during insertion into the artery and improvethe ease of advancement of the device through the vasculature. Thehydrophilic coating can be limited to the working portion of the device.In an embodiment, the distal portion of the shaft is dip-coated with apolymer material such as polyurethane. The dip coating may have gradualtransitions between sections of varying thickness moving along thelength of the device. In an embodiment, the distal coating is limited tothe distal-most 0.5 cm to 3 cm of the elongated sheath body 222, so thatit facilitates insertion without compromising security of the sheath inthe puncture site or the ability of the operator to firmly grasp thesheath during insertion. In an alternate embodiment, the sheath has nocoating. The access sheaths described herein may also include aradiopaque tip marker to facilitate placement of the device usingfluoroscopy. For example, FIG. 3 shows the access sheath 220 having aradiopaque tip marker 230. In an example the radiopaque tip marker is ametal band, for example platinum iridium alloy, embedded near the distalend of the sheath body 222 of the access sheath 220. Alternately, theaccess sheath tip material may be a separate radiopaque material, forexample a barium polymer or tungsten polymer blend.

As mentioned above, the arterial access device systems described hereincan include one or more tapered dilators to improve entry into theartery. The entry or distal tip of the arterial access sheaths describedherein can be tapered so as to allow smooth introduction of the sheathover a guide wire into the artery. The distal tip of the arterial accesssheath itself can be configured such that when the access sheath isassembled with the sheath dilator to form a sheath assembly, the sheathassembly can be inserted smoothly over the sheath guide wire through thearterial puncture with minimal resistance. FIG. 5 shows a sheath dilator260 that can be an elongated body inserted into the artery and enablessmooth insertion of the access sheath 220 over the sheath guidewire 300through a puncture site in the arterial wall. Thus, the distal end ofthe dilator 260 can be generally tapered to allow the dilator to beinserted over the sheath guidewire 300 into the artery, and to dilatethe needle puncture site to a larger diameter for insertion of theaccess sheath 220 itself. To accommodate these functions, the dilator260 can have a tapered end 268 with a taper that is generally between 6and 12 degrees total included angle (relative to a longitudinal axis ofthe dilator), with a radiused leading edge. Sheath dilators can belocked to the access sheath when assembled for insertion into theartery. For example, a proximal hub 264 of the sheath dilator 260 can bestructured to snap into or over a corresponding structure on thearterial access sheath 220, such as the proximal hub 224 having thehemostasis valve 226. An inner lumen of the dilator 260 can accommodatea sheath guidewire 300, with an inner diameter of between 0.037″ to0.041″, depending on the sheath guide wire size for example.

In an embodiment, the arterial access device may be supplied in a kitthat includes two or more tapered dilators. The first tapered dilator isused with the arterial access device to gain entry into the artery, forexample the tapered dilator 260 of FIG. 5, and is thus sized andconstructed in a manner similar to standard introducer sheath dilators.Example materials that may be used for the tapered dilator include, forexample, high-density polyethylene, 72D Pebax, 90D Pebax, or equivalentstiffness and lubricity material. A second tapered dilator may besupplied with the arterial access device, with a softer distal sectionor a distal section that has a lower bending stiffness relative to thedistal section of the first tapered dilator. That is, the second dilatorhas a distal region that is softer, more flexible, or articulates orbends more easily than a corresponding distal region of the firstdilator. The distal region of the second dilator thus bends more easilythan the corresponding distal region of the first dilator. In anembodiment, the distal section of the first dilator has a bendingstiffness in the range of 50 to 100 N-mm² and the distal section of thesecond dilator has a bending stiffness in the range of 5 to 15 N-mm².

The second dilator (which has a distal section with a lower bendingstiffness) may be exchanged with the initial, first dilator such thatthe arterial access device may be inserted into the internal carotidartery and around curvature in the artery without undue force or traumaon the vessel due to the softer distal section of the second dilator.The distal section of the soft, second dilator may be, for example, 35or 40D Pebax, with a proximal portion made of, for example 72D Pebax. Anintermediate mid portion or portions may be included on the seconddilator to provide a smooth transition between the soft distal sectionand the stiffer proximal section. In an embodiment, both dilators mayhave radiopaque tip markers so that the dilator tip position is visibleon fluoroscopy. In an embodiment, the distal most edge of one or bothcatheters is atraumatic and configured to reduce the likelihood of thedistal most edge damaging or cutting tissue while being moved throughthe artery. The distal most edge may be rounded or may have any shapethat reduces the likelihood of the distal most edge damaging tissue.

To facilitate exchange of the first dilator for the second dilator, oneor both dilators may be constructed such that the distal section of thedilator is constructed from a tapered single-lumen tube, but theproximal portion of the dilator and any adaptor on the proximal end hasa side opening. FIG. 19 shows an example of a dilator 4005 which isformed of an elongated member sized and shaped to be inserted into anartery, and a proximal hub 4020. The dilator has a side opening 4010,such as a slot, that extends along at least a portion of the length ofthe dilator 4005 such as along the elongated body and the proximal hub4020. In an embodiment, the side opening 4010 is located only on aproximal region of the dilator 4005 and through the proximal hub 4020although this may vary. The side opening 4010 provides access to aninternal lumen of the dilator 4005, such as to insert and/or remove aguidewire into or from the lumen. An annular, movable sleeve 4015 with aslot on one side is located at or near the proximal hub 4020 of thedilator 4005. The sleeve 4015 may be moved, such as via rotation, abouta longitudinal axis of the hub 4020, as described below. Note that thedistal end of the dilator 4005 has a tapered configuration for dilatingtissue.

FIG. 20 shows an enlarged view of the proximal region of the dilator4005. As mentioned, the dilator 4005 has a side opening 4010 in the formof a slot that extends along the length of the dilator 4005 and theproximal hub 4020. The sleeve 4015 is positioned around the outerperiphery of the dilator and is shaped such that it covers at least aportion of the side opening 4010. Thus, the sleeve 4015 can prevent aguidewire positioned inside the dilator 4005 from exiting the dilatorvia the side opening 4010. As mentioned, the sleeve 4015 is movablerelative to the dilator 4005 and proximal hub 4020. In the illustratedembodiment, the sleeve 4015 is rotatable about a longitudinal axis ofthe dilator 4005 although other types of relative movement are withinthe scope of this disclosure. As shown in FIG. 21, the sleeve 4015 has aslot 4210 that can be aligned with the side opening 4010. When alignedas such, the slot 4210 and side opening 4010 collectively provide anopening for a guidewire to be inserted or removed from the internallumen of the dilator 4005. The sleeve 4015 can be rotated between theposition shown in FIG. 20 (where it covers the side opening 4010) andthe position shown in FIG. 21 (where the side opening is uncovered dueto the slit 4210 being aligned with the side opening 4010.)

A method of use of this embodiment of an arterial access device kit isnow described. A guide wire, such as an 0.035″ guidewire, is insertedinto the common carotid artery, either using a Modified Seldingertechnique or a micropuncture technique. The distal end of the guidewirecan be positioned into the internal or external carotid artery, or stopin the common carotid artery short of the bifurcation. The arterialaccess device with the first, stiffer dilator, is inserted over the0.035″ wire into the artery. The arterial access device is inserted suchthat at least 2.5 cm of sheath is in the artery. If additional purchaseis desired, the arterial access device may be directed further, and into the internal carotid artery. The first dilator is removed whilekeeping both the arterial access device and the 0.035″ wire in place.The side opening 4010 in the proximal portion of the dilator allows thedilator to be removed in a “rapid exchange” fashion such that most ofthe guidewire outside the access device may be grasped directly duringdilator removal. The second dilator is then loaded on to the 0.035″ wireand inserted into the sheath. Again, a dilator with a side opening 4010in the proximal portion of the dilator may be used to allow the 0.035″wire to be grasped directly during guide wire insertion in a “rapidexchange” technique. Once the second dilator is fully inserted into thearterial access device, the arterial access device with the softertipped, second dilator is advanced up the internal carotid artery andaround bends in the artery without undue force or concern for vesseltrauma. This configuration allows a more distal placement of thearterial access device without compromising the ability of the device tobe inserted into the artery.

Alternately, one or more standard dilators may be used without sideopenings. If a standard dilator without a side opening is used, afterthe access device is inserted into the artery over a guide wire with thefirst dilator, the first dilator may be removed together with theguidewire, leaving only the access device in place. The second dilatorwith a guide wire preloaded into the central lumen may be insertedtogether into the arterial access device. Once fully inserted, theaccess device and second dilator with softer tip may be advanceddistally up the internal carotid artery as above. In this alternatemethod, the initial guide wire may be used with both dilators, or may beexchanged for a softer tipped guide wire when inserted with the secondsofter tipped dilator.

Catheter Exemplary Embodiments

Described herein are catheters configured to be inserted through anarterial access device. Examples of catheters are described in U.S.Provisional Application Ser. No. 62/029,799, filed Jul. 28, 2014 andU.S. Provisional Application Ser. No. 62/075,101 entitled “TranscarotidNeurovascular Catheter” and filed Nov. 4, 2014, which are bothincorporated by reference herein in their entirety.

As described above, FIGS. 1, 2 and 3 illustrates embodiments of acatheter 2030 that is configured to be inserted through an arterialaccess device 2010 into the common carotid artery (CCA), and from thereadvanced to a target treatment area in the internal carotid artery orcerebral artery. 22 shows a schematic view of an exemplary catheter 105.The catheter 105 has an external dimension that is sized and shaped forinsertion into a blood vessel. A proximal hub 2065 has a female Luerconfiguration for attachment of a syringe during prep and attachment ofother components. For example a separate hemostasis valve may beattached to proximal hub 2065, to allow introduction of devices such asa microcatheter, guide wire, or thrombectomy device while preventing orminimizing blood loss during the procedure. Alternately, the hemostasisvalve may be integral to the catheter proximal adaptor. In anembodiment, this valve is an adjustable-opening valve such as aTuohy-Borst or rotating hemostasis valve (RHV). In another embodiment,the valve is a passive seal hemostasis valve.

The catheter 105 may be made with a two or more layer construction. Inan embodiment, the catheter has a PTFE inner liner, an outer jacketlayer, and at least a portion of the catheter has a reinforcementstructure, such as a tubular structure formed of, for example, a woundcoil, braid or cut hyptotube. In addition, the catheter may have aradiopaque marker at the distal tip to facilitate placement of thedevice using fluoroscopy.

The catheter 105 has an insertable portion (i.e. working length) that issized to be inserted through an access sheath in the carotid artery andpassed through an arterial pathway (through the artery) to the distalICA or cerebral vessels. In an embodiment the catheter 105 has a workinglength ranging from 40 to 70 cm. In an embodiment, the catheter has aworking length of less than 70 cm, less than 60 cm, or less than 50 cm.Alternately, the length of catheter can be defined relative to thelocation of the access site and the target cerebral artery site. In anembodiment, the catheter is configured to be introduced into the arteryat a location in the artery that is less than 40 cm, less than 30 cm, orless than 20 cm from the location of the target site as measured throughthe arterial pathway. The distance may further be defined by a ratio ofworking length to the distance between the location where the catheterenters the arteriotomy and the target site. In an embodiment, this ratiois less than 2×. In an embodiment, the working portion of the device mayhave a hydrophilic coating to improve the ease of advancement of thedevice through the vasculature. In an embodiment, at least 40% of theworking length of the catheter is coated with a hydrophilic material. Inother embodiments, at least 50% or at least 60% of the working length ofthe catheter is coated with a hydrophilic material.

In an embodiment, the distal-most portion is constructed to be moreflexible than the proximal portion, with one or more flexible sections,to successfully navigate the internal carotid artery curvature to reachtarget sites in the distal ICA or cerebral arteries. The shaft may havea transition section of one or more increasingly stiff sections towardsthe more proximal section of the shaft, with the proximal most portionhaving the stiffest shaft section. Alternately, the transition sectionis a section of continuously variable stiffness from the distal sectionstiffness to the proximal section stiffness. In an embodiment, thedistal most flexible section is 5 to 15 cm, a transition section is 5 to15 cm, and a proximal stiff section takes up the remainder of theworking length. In an embodiment where the catheter has a working lengthof 40 cm, the proximal stiff section is in a range 10 to 30 cm. In anembodiment where the catheter has a working length of 70 cm, theproximal stiff section is in a range from 40 to 60 cm.

Alternately, the flexible distal section and transition section may bedescribed as a portion of the overall catheter working portion whereinthe working portion is the portion that is configured to be insertedinto an artery. In an embodiment, the flexible distal section may bebetween 3 to 10% of the length of the working portion of the catheterand the transition section may be between 15-35% of the length of theworking portion of the catheter. In other embodiments, the distalsection is at least 20% or at least 25% of the length of the workingportion of the catheter.

In an embodiment, the flexibility of the distal most section is in therange 3 to 10 N-mm² and the flexibility of the proximal post section isin the range 100 to 500 N-mm², with the flexibility/flexibilities of thetransition section falling between these two values.

As noted above, the catheter may have sections with discreet and/orcontinuously variable stiffness shaft. The sections of varyingflexibility may be achieved by multiple methods. For example, the outerjacket layer may be composed of discreet sections of polymer withdifferent durometers, composition, and/or thickness. In anotherembodiment, the outer layer has one or more sections of continuouslyvariable outer layer material that varies in flexibility. The cathetermay be equipped with the continuously variable outer layer material bydip coating the outer layer rather than laminating a jacket extrusiononto a PTFE-liner and reinforcement assembly of the catheter. The dipcoating may be, for example, a polymer solution that polymerizes tocreate the outer jacket layer of the catheter. The smooth transitionfrom one flexibility (e.g., durometer) to another flexibility along thelength of the catheter can be accomplished via dipping the catheterassembly in multiple varying durometer materials whereby the transitionfrom one durometer to another can be accomplished in a graded pattern,for example by dipping from one side of the catheter in one durometerwith a tapering off in a transition zone, and dipping from the otherside in another durometer with a tapering off in the same transitionzone, so there is a gradual transition from one durometer to the other.In this embodiment, the dip coating can create a thinner walled outerjacket than a lamination assembly. In another embodiment, the catheterhas an outer jacket layer that is extruded with variable durometer alongthe length, to provide variable flexibility along the length of thecatheter.

In an embodiment, at least a portion of the catheter has a reinforcementstructure, such as a tubular structure formed of, for example, a woundcoil, braid that is composed of discreet or continuously varyingstructure to vary the stiffness, for example a variable coil or braidpitch. In an embodiment, the reinforcement structure is a cut hyptotube,with a cut pattern that is graded along the length, for example cut in aspiral pattern with continuously variable pitch or continually variablecut gap, or a repeating cut pattern that allows the tube to flex wherebythe repeating pattern has a continuously variable repeat distance orrepeat size or both. A cut hypotube-reinforced catheter may also havesuperior pushability than a coil-reinforced catheter, as it is astructure with potentially greater stability in the axial direction thana wound coil. The material for the reinforcement structure may bestainless steel, for example 304 stainless steel, nitinol, cobaltchromium alloy, or other metal alloy that provides the desiredcombination of strengths, flexibility, and resistance to crush. In anembodiment, the reinforcement structure comprises multiple materialsalong the different sections of flexibility

In another embodiment the catheter has a PTFE inner liner with one ormore thicknesses along variable sections of flexibility. In anembodiment, the PTFE inner liner is constructed to be extremely thin,for example between 0.0005″ and 0.0010″. This embodiment provides thecatheter with a high level of flexibility as well as the ability toconstruct a thinner-walled catheter. For example, the PTFE liner isconstructed by drawing a mandrel through a liquid PTFE liquid solutionrather than the conventional method of thin-walled PTFE tubingmanufacture, namely extrusion of a PTFE paste which is then dried andsintered to create a PTFE tube. The draw method allows a very thin andcontrolled wall thickness, such as in the range of 0.0005″-0.0010″.

Any one of the aforementioned manufacturing methods may be used incombination to construct the desired flexibility and kink resistancerequirement. Current tri-layer catheters have wall thicknesses rangingfrom 0.005″ to 0.008″. These manufacturing techniques may results in acatheter with better catheter performance at the same wall thickness, orwith equal or better catheter performance at lower wall thicknesses forexample between 0.003″ to 0.005″.

In an embodiment, the distal flexible section of the catheter may beconstructed using one or more of: a dip coated outer layer, an extremelythin drawn PTFE layer, and a cut hypotube reinforcement layer, with agradual transition from the flexible section to a stiffer proximalsection. In an embodiment, the entire catheter is constructed with oneor more of these elements

In some instances, there is a need to reach anatomic targets with thelargest possible internal lumen size for the catheter. For example thecatheter may be used to aspirate an occlusion in the blood vessel. Thusthere is a desire to have a very flexible, kink resistant and collapseresistant catheter with a thin wall and large inner diameter. A catheterusing the construction techniques disclosed herein meets theserequirements. For example, the catheter may have an inner diameter of0.070″ to 0.095″ and a working length of 25-50 cm. In anotherembodiment, the catheter may be sized to reach the more distal cerebralarteries, with an inner diameter of 0.035″ to 0.060″ and a workinglength of 40-80 cm. In an embodiment, the catheter is configured tonavigate around a 180° bend around a radius as small as 0.050″ or 0.100″without kinking, wherein the bends are located within 5 cm, 10 cm, or 15cm of the arteriotomy measured through the artery. In an embodiment, thecatheter can resist collapsing whilst in a tortuous anatomy up to180°×0.050″ radius bend without collapsing when connected to a vacuum upto 20 inHg. In an embodiment, the catheter can resist collapse in thesame conditions when connected to a vacuum up to 25 inHg.

In another embodiment, the inner and/or outer diameter of the catheteris stepped up at a proximal region of the catheter such that theproximal region of the catheter has a larger inner and/or outer diameterthan a remaining distal region of the catheter. FIG. 23 shows anembodiment with a distal portion 2070 with one inner and outer diameter,and a proximal portion 2075 with a larger inner and outer diameterrelative to the distal portion. In one embodiment, the length of thedistal portion of the catheter is configured to be placed in smallerdistal vessels, whereas the larger proximal portion will reside in moreproximal, larger vessels. In this embodiment, the catheter may have onediameter for the distal 10-25 cm, then have a step up in diameter ofbetween 10-25% for the remainder of the working length. The step upwould occur over a tapered transition section between 3 and 10 mm inlength, depending on the size of the step up and the need to make asmooth transition. Alternately, the catheter is used with a steppedsheath with a larger diameter proximal region such as the embodiment ofFIG. 8 or a sheath with a larger diameter proximal extension as in FIG.10. In this case, the catheter may be stepped up a length and diameterto match the stepped sheath. For example, if the sheath has a portionwith larger diameter for the proximal 20 cm of the sheath, the catheterwould have a larger diameter for a longer length such as the proximal 25cm to allow for additional length through proximal adaptors and valvessuch as an RHV. The remaining distal region would have a smallerdiameter, with a step up over a tapered transition section between 3 and10 mm in length, depending on the size of the step up and the need tomake a smooth transition.

In some instances, the catheter is used to aspirate a clot in an artery.FIGS. 24 A-D show examples of catheters having non-square distal tips ordistal edges. With reference to FIG. 24A, the distal region of acatheter 105 is shown. The catheter 105 has a distal-most tip or edge210 that forms an opening 215 at the distal end of the catheter 105. Thedistal edge 210 forms an angle that is non-perpendicular relative to thelongitudinal axis L. Such a tip defines a different sized opening 215than if the tip were perpendicular to the axis L. That is, the opening215 is larger and presents a larger suction area relative to a distaltip that is cut normal to the longitudinal axis. The catheter thereforemay provide a larger suction force on the occlusion located near thetip. The larger area opening 215 also facilitates suctioning the clotinto the lumen of the catheter, rather than just capturing the clot atthe tip with suction force and pulling back the captured clot with thecatheter. In FIG. 24A, the catheter 105 has an angled, straight edge 210creating an elliptical opening 215. In FIGS. 24B, 24C, and 24D, thedistal edge 210 is curved or non-straight such that the distal opening215 is non-planar and may offer greater opening without extending thetip length out as much, which may optimize the contact area with theocclusion further. The distal edge 210 may be straight, curved,undulating, or irregular. In an embodiment with a cuthypotube-reinforced catheter, the distal tip of the hypotube can beformed with the non-square shape. In an embodiment with a radiopaquemarker band, the radiopaque marker band may have a non-square edge whichcan then be used to create the non-square catheter tip shape.

A cause of difficulty in advancing catheters through severe bends andacross side branches is the mismatch between the catheter and the innerguiding components such as smaller catheters, microcatheters, orguidewires. One technique for advancing a catheter is called a tri-axialtechnique in which a smaller catheter or microcatheter is placed betweenthe catheter and the guide wire. However, with current systems thesmaller catheter has a diameter mismatch between either the largercatheter, the guide wire, or both, which creates a step in the system'sleading edge as the system is advanced in the vasculature. This step maycause difficulty when navigating very curved vessels, especially at alocation where there is a side-branch, for example the ophthalmicartery. In an embodiment, as shown in Figure A, the catheter 105 issupplied with a tapered co-axial inner member 2652 that replaces thesmaller catheter generally used. The inner member 2652 is sized andshaped to be inserted through the internal lumen of the catheter. Theinner member 2652 has a tapered region with an outer diameter that formsa smooth transition between the inner diameter of the catheter 203 andthe outer diameter of a guidewire 2515 or microcatheter that extendsthrough an internal lumen of the inner member 2652. In an embodiment,the tapered dilator or inner member 2652, when positioned within thecatheter, creates a smooth transition between the distal-most tip of thelarger catheter 105 and the outer diameter of a guide wire 2515 whichmay be in the range of 0.014″ and 0.018″ diameter for example. Forexample, the inner luminal diameter may be between 0.020″ and 0.024″. Inanother embodiment, the inner diameter is configured to accept amicrocatheter with an outer diameter in the range of 0.030″ to 0.040″ oran 0.035″ guide wire in the inner lumen, for example the inner luminaldiameter may be 0.042″ to 0.044″.

In a variation of this embodiment, shown in FIG. 25B, in addition to thetapered region, the inner member 2652 includes an extension formed of auniform diameter or a single diameter, distal-most region 2653 thatextends distally past the tapered portion of the inner member 2652. Inthis embodiment the distal region 2653 of the inner member 2652 mayperform some or all of the functions that a microcatheter would doduring an interventional procedure, for example cross an occlusion toperform distal angiograms, inject intraarterial agents, or deliverdevices such as aneurysm coils or stent retrievers. In this manner, amicrocatheter would not need to be exchanged for the dilator for thesesteps to occur.

The material of the dilator (inner member 2652) is flexible enough andthe taper is long enough to create a smooth transition between theflexibility of the guide wire and the catheter. This configuration willfacilitate advancement of the catheter through the curved anatomy andinto the target cerebral vasculature. In an embodiment, the dilator isconstructed to have variable stiffness, for example the distal mostsection is made from softer material, with increasingly harder materialstowards the more proximal sections. In an embodiment, distal end of thetapered dilator has a radiopaque marker such as a platinum/iridium band,a tungsten, platinum, or tantalum-impregnated polymer, or otherradiopaque marker.

In another embodiment, a catheter system includes an anchor device whichis configured to be easily navigable through the vasculature to alocation distal to the cerebral occlusion. When the anchor is deployed,it may be used as a rail and counter force to facilitate advancement ofthe catheter to the proximal face of the occlusion. In an example shownin FIG. 26, the anchor is a microcatheter 2505 with a distal balloon2510. The microcatheter 2505 is placed over a guidewire 2515 to a sitedistal of the target treatment area, for example a thrombus 10, and thenthe distal balloon 2510 is inflated. Alternately, the microcatheter hasan atraumatic guidewire tip built in and is advanced as a stand-alonedevice. The catheter 2030 can then use the shaft of the microcatheter2505 as a rail to be advanced towards the treatment site, as is done inconventional techniques. However, because the balloon 2510 is inflated,the distal end of the microcatheter 2505 is anchored against the vesselwall and provides counter force to the advancing catheter 2030. Theguidewire 2515 remains in place during this maneuver, such that if theanchor (i.e., the balloon 2510) and catheter 2030 need to bere-advanced, access is maintained across the treatment site with theguide wire 2515.

The atraumatic distal anchor can be a device other than a balloon. Forexample, other atraumatic distal anchors may include microcatheters withmechanically expandable-tips such as a braid, coil, or molly-boltconstruction. The expandable tip can be configured to be sufficientlysoft and to provide sufficient force along a length of the microcatheterso as to reduce focal pressure against the vessel wall and minimizevessel wall injury.

Another variation of this embodiment as shown in FIG. 27 is a guidewire2615 with an expandable tip 2620 such as a balloon or expandable cage orstent. The guidewire 2615 may be placed in the vasculature using amicrocatheter and then deployed when the microcatheter is retracted. Theexpandable portion of the guidewire 2615 device may be formed fromseparate braided filaments or cut from a single hypotube and expand witha counterforce actuating member. For example the proximal end of theexpandable tip may be attached to the distal end of a hollow hypotube,and the distal end attached to a wire which runs the length of thehypotype. When the wire is pulled back, the expandable tip is shortenedin length and expanded in diameter. Pushing the wire forward wouldcollapse the expandable tip.

In another embodiment, shown in FIG. 28, the catheter and the arterialaccess device are combined to be a single device 2710 with a continuouslumen extending through the length of the device. A proximal portion2720 comprises the arterial access sheath and a distal portion 2730functions as the catheter. The embodiment may include an occlusionballoon 2715 located between the distal and proximal portion. The distalportion 2730 is constructed to be more suited for navigating thecerebral vasculature. In particular, the distal portion 2730 is moreflexible and tapered to a smaller diameter than the proximal portion2720.

In another embodiment, as shown in FIGS. 29 and 30, the catheter has asecond lumen to maintain guide wire access to facilitate re-advancementor exchange of the catheter without recrossing the target anatomy. In anembodiment, shown in FIG. 29, the catheter has two lumens whichterminate together at the distal tip: a main lumen and a secondguidewire lumen. The termination may be such that a distal-facingsurface is arranged at an angle (relative to the longitudinal axis ofthe catheter), to facilitate tracking of the catheter through thevasculature. In another embodiment, shown in FIG. 30, the secondguidewire lumen is inside an extension 1247 that extends out past thetermination of the main lumen. The extension 1247 is a distal-mostregion of the catheter that protrudes distally past an opening formed bythe main lumen. The extension 1247 forms a shaft having a reduced outerdiameter relative to the outer diameter of the catheter around the mainlumen. The second lumen is smaller than the shaft of the main catheter,and may be positioned in or across an occlusion while the distal end ofthe main lumen is positioned on the proximal face of an occlusion. Thedistal end of the main lumen may be terminated at an angle as well, tofacilitate tracking of the device.

In some instances, it may be desirable for the catheter to have andistal tip which can increase in diameter after being positioned at atarget treatment site, for example to facilitate removal of an occlusionwhen an aspiration device is connected to the proximal portion of thecatheter. In an embodiment, the catheter has an expandable tip portion.The expandable tip portion may be constructed with a mechanicalstructure such as a braid or stent structure, which can open or close ina repeatable manner. The mechanism for opening the tip may be apull-wire which shortens the expandable portion, or an outer retentionsleeve which maintains the distal section in a small diameter but whenretracted allows the distal tip to expand. The distal section may becovered with a membrane such that when aspiration is applied, eitherwith the tip expanded or not, a vacuum may be applied at the very tip ofthe catheter. The expandable tip allows the catheter to maintain a smallprofile during tracking of the catheter to the target anatomy, but thenexpands the distal luminal area for facilitated capture of occlusivematerial such as thrombus. The thrombus, once captured into thecatheter, may be sucked all the way into the aspiration device, oralternately will be lodged in the lumen of the catheter where thecatheter is no longer expanded, and at that point can be removed byretraction of the entire catheter.

In another embodiment, shown in FIG. 31A, the catheter 2830 is atelescopic attachment to the distal portion of the arterial accessdevice 2820. In this regard, the catheter can be formed of two or moreconcentric, tubular sections that telescopically slide relative to oneanother to increase and/or decrease the entire collective length of themovably attached tubular sections. The distal region of the arterialaccess device 2820 has one or more structures that telescopically extendin the distal direction along the longitudinal axis of the arterialaccess device. The structures may also be telescopically collapsed suchthat they do not extend past the distal end of the arterial accessdevice. When the structures are telescopically expanded past the distalend of the arterial access device, the structures collectively form acontinuous inner lumen. A tether element such as a wire 2835 may beconnected to the proximal end of the catheter 2830 and extends out theproximal end of arterial access device such that the telescopingactuation may be accomplished by pushing or pulling the tether elementfrom the proximal end of the arterial access device. Thus the tetherelement must be of sufficient rigidity to push the catheter withoutbuckling. The junction between the tether element 2835 and the catheter2830 includes a transition zone that bridges the flexibility of thecatheter and the rigid tether element, so as to avoid kinking duringactuation of the telescoping catheter. For example the tether elementmay be flattened, ground down, or further down-sized to be more flexibleat the transition zone, and/or the catheter may be made more rigid viareinforcement construction or material selection. An occlusion member,such as balloon 2815, may be positioned on the arterial access device2820 or catheter 2830. Both the access device 2820 and catheter 2830 hasa distal radiopaque marker. Additionally, the catheter has a radiopaquemarker at the proximal end where the tether 2835 joins the catheter, sothat the user may visualize the distance between the distal end of theaccess device and the proximal end of the catheter, and thereforevisualize the overlap region between the two.

It may be sufficient for the contact area between the overlappingportion of the arterial access device 2820 and the catheter 2830 toprovide sufficient seal such that the aspiration or pressure force istransmitted to the distal end of the catheter 2830 with no leakage atthe junction between the two devices. However, if additional sealing isneeded, the system may include a sealing element at the juncture betweenthe arterial access device 2820 and the catheter 2830. This embodimentis also useful if multiple size catheters are required during aprocedure to reach different target sites, without the necessity ofreplacing the arterial access device. The sealing element of a smallercatheter 2830 can be designed to seal the larger gap between thecatheter and the access device. One embodiment of a seal element isshown in FIG. 31B. A sealing element 2845 may be positioned on theexternal surface of the proximal end of the catheter 2830. In anembodiment, the sealing element 2845 is one or more external ridgefeatures manufactured from an elastomeric material, and which iscompressed when the catheter 2830 is inserted into the lumen of thearterial access device 2820. The ridge geometry is such that it behavesas an O-ring, quad ring, or other piston seal design. FIG. 31C shows asimilar configuration, with the sealing element 2845 having a wiper sealconfiguration such as an inclined surface that is biased against aninner surface of the arterial access device 2820. Alternately, the seal2845 may be an inflatable or expandable member such as a balloon orcovered braid structure that can be inflated or expanded and providesealing between the two devices at any time, including after thecatheter 2830 is positioned at the desired site. An advantage to thisembodiment is that there is no sealing force being exerted on thecatheter during catheter positioning, but rather is applied after thecatheter is positioned. Alternately, the sealing element is on the innerof the distal end of the arterial access device 2820, with structuressimilar to those described above.

In an embodiment, the arterial access device 2820 and catheter 2830 withfeatures to allow the two to be telescopically coupled as in FIG. 31Aare supplied together in a kit. In an embodiment, the kit also includesa sheath dilator and sheath guidewire to aid in insertion of thearterial access device through a puncture into the artery. In anexemplary embodiment configured for transcarotid access into thecarotid, the arterial access device has insertable portion between 15-30cm in length, and the telescoping catheter is 10 to 15 cm in length. Inan alternate exemplary embodiment, the arterial access device is a longsheath configured to be positioned into the carotid artery from atransfemoral access site. In this embodiment, the arterial access deviceis between 90 and 120 cm in working length, and the telescoping catheteris 10 to 25 cm in length. In either case, the tether is of a length thatallows manipulation of the catheter 2830 when positioned to its fulllength extending from the arterial access device 2820. In an embodiment,the kit also includes a sheath dilator and a sheath guide wire toposition the arterial access device in the carotid artery. In anembodiment the kit also includes an inner tapered sheath such as thatshown in FIG. 25A or FIG. 25B to aid in telescopingly positioning thecatheter 2830.

In an embodiment, the arterial access device 2820 is a 6F sheath sizewith ID about 0.086″ to 0.088″, and the catheter 2830 has an outerdiameter of between 0.083″ and 0.086″ and an inner diameter of between0.068″ and 0.072″. In an alternate embodiment, the arterial accessdevice 2820 is a 5F sheath size with ID about 0.074″ to 0.076″, and thecatheter 2830 has an outer diameter of between 0.071″ and 0.073″ and aninner diameter of between 0.058″ and 0.062″. Other diameter combinationsare possible as warranted by the procedure.

In another embodiment, the catheter 2830 includes a structure formorcelating the thrombotic occlusion as it is being aspirated into thecatheter. In an embodiment, a separate thrombus disruption device withan expandable distal segment is inserted into the catheter andpositioned inside the lumen near the distal tip, once the catheter ispositioned at the target site and the inner guide wire and/or innercatheter or dilator are removed. The device is inserted with theexpandable segment in the collapsed state and the expanded proximal tothe distal tip of the catheter. The device is configured to be smallenough in this state that it should have minimal interference withthrombus aspiration. In an exemplary method, the thrombus disruptiondevice is connected to a rotary motor at the proximal end such that theexpandable portion is rotating at the distal segment of the catheter.Aspiration is then initiated at the proximal end of the catheter. Asthrombus is aspirated into the catheter, the rotating expandable sectionbreaks up the clot which is then easily aspirated through the length ofthe catheter. Alternately, the thrombus disruption device is expandedbut remains still and is only rotated or translated back and forth afteraspiration has started and if and when the clot becomes stuck in thelumen of the catheter. In an embodiment, the device also includes ashort atraumatic distal tip, such as a floppy tip on a neurovascularguide wire. This feature minimized the chance of this device causingvascular injury should it protrude from the distal end of the catheterat any time during its use.

In an embodiment, the thrombus disruption device is manufactured from agenerally elongate structure, coupled with an inner member attached atthe distal end to actuate the expandable segment. The construction ofthe expandable segment may be a braid, one or more helical wires, or atube with a cut pattern, any of which are designed to expand whenshortened by pulling the inner member. Alternately, as shown in FIG. 51,the thrombus disruption device 5105 is formed of a generally elongatestructure, coupled with a retractable sleeve 5110 that constrains theexpandable segment during delivery. The construction of the expandablesegment may be a braid, one or more helical wires, or a tube with a cutpattern, or a brush-type structure that is designed to expand when theconstraining retractable sleeve is retracted, as seen in FIG. 52. Theretractable sleeve 5110 may be a microcatheter. If the device is to berotatable, the shaft of the device can transmit torque, such as abraid-reinforced construction, a counter-wound coil construction, or thelike. As with the catheter, the device is very flexible at the distalend for navigation into the intracranial and cerebral anatomy, withincreasingly stiff properties as one moves towards the proximal end, sothat the device can be easily delivered, the expandable section quicklyactuated. If a thrombotic piece T is caught in the tip of the catheter2830, as seen in FIG. 53, the device 5105 is rotated as indicated by thearrow R, or moved back and forth as required to break up the thrombus,or alternately the device 5105 is rotated throughout the aspiration stepto ensure that the clot is never clogging the distal tip of the catheterbut is immediately broken up once aspirated into the distal tip.Aspiration as indicated by the arrows A is maintained throughout thismaneuver to ensure that the morecelated thrombus is removed via thecatheter 2830 and not re-inserted into the blood stream.

Many of the catheter configurations described herein provide a benefitin aspiration ability over existing methods and devices particularlywhen the cathereter is combined with one of the disclosed arterialaccess devices. This benefit translates to more rapid and more effectiveremoval of thrombotic occlusion and reduced distal emboli in thetreatment of strokes. This benefit is derived at least from from shorterand in some cases larger inner lumen diameter aspiration catheterdesigns. According to Poiseuille's law for laminar flow in a tube, theflow rate can be expressed as the equation Q=π×r4×(AP)/8×n×L, whereQ=flow rate, r=radius of the tube, P=pressure, n=viscosity, andL=length. As shown by this equation, flow rate drops by increases inlength and drops proportionally by decreases in radius to the fourthpower. The transcarotid embodiments described herein allow aspirationrates through catheters about half the length, and therefore potentiallytwice the flow with respect to prior devices. In addition, theembodiments disclosed herein allow larger diameter catheters the abilityto reach the same target sites more easily and more often, due to thegreater proximal support from the transcarotid access site, the greatercatheter pushabiltiy due to the more distal transition from flexible tostiff segments, and the tapered inner members as in FIGS. 25A and 25B,among other features.

For example, one catheter currently used for clot aspiration is theNavien 058 or the Navien 072 catheters (sold by Covidien). Thesecatheters have inner diameters of 0.058″ and 0.072″ respectively andlengths of 115 and 105 cm respectively. Although the Navien 072 catheterhas been demonstrated to be a more effective catheter for removal ofcerebral thrombus, it is less often able to reach the target site. Incontrast, the Penumbra 5Max and 5Max ACE are frequently able to reachthe face of the clot, and additionally has a stepped configuration thatoffers some diameter benefit. However, these catheter configurationsstill do not perform as well as the catheters disclosed herein.Catheters configured for transcarotid delivery, as in FIG. 22, provideaspiration benefit. Catheters that are both stepped and configured fortranscarotid delivery, as in FIG. 23, provide even more benefit.Finally, a telescoping configuration as in FIG. 31A offers benefit in atransfemoral configuration and even more benefit in a transcarotidconfiguration. These benefits are calculated according to Poiseuille'slaw assuming a fluid viscosity n of 3.7 centipoise (the equivalent oftypical human blood viscosity at body temperature), as shown in thetables in FIG. 54 for the smaller catheter sizes, and FIG. 55 for thelarger catheter sizes.

When different catheter systems are tested for actual aspiration ratesthis benefit is diminished somewhat as compared to the theoreticalaspiration rates, especially at higher flow rates. This is reflective ofthe fact that at the higher flow rates, the flow is less and lesslaminar, and thus lower than the theoretical flow as predicted byPoiseuille's law. However, the shorter and larger ID catheters do show arelative benefit. In an exemplary test method, the catheters are testedfor aspiration rates with a 40% glycerin mixture to simulate theviscosity of blood using the following method: each catheter wasconnected to a stopcock and thence to a 30 cc locking syringe. The tipof the catheter was positioned in a container of the glycerin mixture.The catheter and syringe were purged of air, the syringe was emptied,and then the stopcock was closed. The locking syringe was then pulledback the full 30 cc volume and locked in place. A timer was started whenthe stopcock was opened, and the time was noted at 5 cc, 10 cc, 15 ccand 20 cc of extracted solution in the syringe. The overall averageextraction rate was calculated based on the slope of the data points andwas roughly linear over the 20 cc volume, indicating a constant vacuumlevel using this method. Results and their relative improvements overthe baseline Navien Catheters are provided in the tables in FIGS. 56 and57.

Exemplary Embodiments of Aspiration and Flow Control

As described above, it is sometime desirable to include aspiration orflow reversal devices or structures to the system. Described herein areaspiration and flow control elements configured to be used with anarterial access device, a guide catheter, and/or a catheter of thedisclosed system. Examples of aspiration and flow control elements aredescribed in U.S. Patent Publication No. 2014/0296868, filed Mar. 21,2014, which is incorporated by reference herein in its entirety. Any orall of the arterial access device 2010 and the catheter 2030 may beconnected to sources of passive or active aspiration via flow lines 2025or 2045 (FIG. 1) on the devices. Additionally, the guide catheter 2105may be connected to sources of passive or active aspiration via flowline 2125 (FIG. 3) on the device. The mode of aspiration may bedifferent for each device.

In FIG. 32, the flow line 2025 of the arterial access device 2010 isconnected to a delivery location, such as a receptacle 3100. A source ofaspiration 3125 may be coupled to the flow line 2025. The receptacle3100 and source of aspiration 3125 may be separate or may be combinedinto a single device such as a syringe. A filter 3418 and/or a checkvalve 3419 may be coupled with flow line 2025. In FIG. 33, the flow line2045 of the catheter 2030 is additionally or alternately connected to aseparate aspiration source 3425 and delivery location, such asreceptacle 3105. The aspiration source 3425 and delivery location may becombined into a single device such as a syringe. A filter 3418 and/or acheck valve 3419 may also be coupled with the flow line 2045.

FIG. 34 shows a system whereby both the arterial access device 2010 andcatheter 2030 are connected to the same aspiration source 3430 via flowlines 2025 and 2045, respectively. A valve 3325 controls which device isconnected to the aspiration source 3430. The valve may enable onedevice, the other device, both devices, or neither device to beconnected to the aspiration source at any given time. The valve may be a3-way or 4-way stopcock. Alternately, the valve may be a flow controllerwith a simple actuation which selects the configuration as describedabove.

In an embodiment, a flow controller may facilitate control of multiplemechanisms of aspiration through multiple devices in a single unit. Thisconfiguration may facilitate use of the system by a single operator. Theflow controller may include one or more control interfaces that a usermay actuate to regulate which device is being aspirated, for example thearterial access device, the catheter, both, or neither. FIG. 35 shows anembodiment of a system that utilizes such a flow controller 3400. Theflow controller 3400 is connected to the flow line 2025 of the arterialaccess device 2010 as well as to the flow line 2045 of the catheter2030. In this manner, the flow lines 2025 and 2045 permit fluid to flowfrom the arterial access device 2010 and the catheter 2030,respectively, to the flow controller 3400. The controller 3400 may beconnected to either or both a passive source of aspiration 3410 and anactive source of aspiration 3420. The flow controller housing 3429contains control mechanisms to determine how and when each device isconnected to each source of aspiration. The control mechanisms may alsocontrol the level of aspiration from each source. In addition, thecontroller may include a control that permits a pulsatile aspirationmode which may facilitate the breaking up and aspiration of the cerebralocclusion. The flow controller may have an interface for switchingbetween continuous and pulsatile aspiration modes. The controlmechanisms may be designed to be operable using one hand. For example,the control mechanisms may be toggle switches, push button switches,slider buttons, or the like. In an embodiment, the flow controller 3400has an interface that can enable the user to restore immediate antegradeflow to the cerebral circulation, for example with a single button orswitch that simultaneously deflates the occlusion balloon on thearterial access device and stops aspiration.

The active source of aspiration may be an aspiration pump, a regular orlocking syringe, a hand-held aspirator, hospital suction, or the like.In one embodiment, a locking syringe (for example a VacLok Syringe) isattached to the flow controller and the plunger is pulled back into alocked position by the user while the connection to the flow line isclosed prior to the thrombectomy step of the procedure. During theprocedure when the tip of the aspiration device (either the arterialaccess device or the catheter) is near or at the face of the occlusion,the user may open the connection to the aspiration syringe. This wouldenable the maximum level of aspiration in a rapid fashion with one user,something that is currently not possible with existing technologies. Inanother embodiment, the aspiration source is a hand-held aspirator whichis configured to be able to aspirate and refill without disconnectingthe aspiration device. In an example of this embodiment, the hand-heldaspirator contains a chamber with a plunger that is moved up and downwith a single-handed actuator. The chamber includes input and outputvalves, such that when the plunger is moved up and down there is acontinuous source of aspiration into and out of the chamber without theneed to remove and empty the chamber as would be needed with a syringe.The chamber input is connected to the catheter, and the chamber outputis connected to a collection receptacle such as blood-collection bag. Inan embodiment, this aspiration source is configured to be used with onehand only.

One disadvantage of current sources of aspiration is that the aspiratedblood is received into an external reservoir or syringe. This blood isgenerally discarded at the end of the procedure, and as such representsblood loss from the patient. In addition, pumps such as centrifugal orperistaltic pumps are known to cause damage to blood cells. Although itis possible to return blood from the external reservoir to the patient,the blood has been exposed to air or has been static for a period oftime, and there is risk of thrombus formation or damage to the bloodcells. Usually, aspirated blood is not returned to the patient to avoidrisk of thromboembolism.

FIG. 36 shows a cross-sectional view of an exemplary aspiration pumpdevice 3250 which is configured not to harm blood cells and which may beconfigured to return blood to the central venous system in real timeduring the procedure, so there is no reservoir in which the bloodremains static. The pump 3250 may be connected to either or both thearterial access device 2010 and catheter 2030. The pump device 3250includes a housing 3215 that encloses a chamber 3220 in which iscontained a portion of the flow line 2025. An expandable portion 3210 ofthe flow line 2025 contained within the chamber 3220 is formed of anelastic material that is at a reduced diameter in its natural state(shown in phantom lines in FIG. 36) but may be configured to change toan expanded diameter (shown in solid lines in FIG. 36). One or moreseals 3125, such as O-rings, seal the interface between the chamber 3220and the flow line 2025. A vacuum source 3230 is coupled to the chamber3220 and is configured to be operated to vary the pressure within thechamber 3220. Two one-way check valves 3235 are located in the flow line2025 on either side of the expandable portion 3210.

In operation of the pump device 3250, the vacuum source 3230 is operatedto create a reduced pressure within the chamber 3220 relative to thepressure within the flow line lumen 3210. The pressure differentialbetween the chamber 3220 and the flow line lumen 3210 causes theexpandable portion 3210 of the flow line 2025 to expand to an increasedvolume within the chamber 3220, as shown in solid lines in FIG. 41. Thisexpansion causes blood to be pulled into the expandable portion 3210from the sheath side of the flow line, shown by the “in” arrow, ascontrolled by the check valves 3235. The vacuum source 3230 may then beturned off so as to normalize the pressure within the chamber 3220. Thiscauses the expandable portion 3210 to revert to its smaller, naturaldiameter, as shown in phantom lines in FIG. 36. The check valves 3235causes the blood within the previously-expanded region of the flow line2025 to be expelled towards location 3120, as shown by the “out” arrowin FIG. 36. The vacuum source 3230 may be operated so as to oscillatethe expandable portion 3210 between the expanded and retracted state andtogether with the one-way check valves 3235 thereby drive fluid throughthe flow line lumen 3210.

FIG. 37 shows a pump system 3305 that includes a pair of pump device3205 a and 3205 b, each of which is of the type shown in FIG. 36. Thatis, each device 3205 includes a housing 3215 that contains a chamber inwhich a portion of the flow line 2025 is contained. The pump devices3205 a and 3205 b are connected in parallel to the flow line 2025 suchthat each pump device 3205 has a flow line 2025 with an expandableportion 3210. The pair of pump devices 3205 a and 3205 b may bealternated between expanded and retracted states to create a relativelycontinuous flow state through the pump system 3305. For example, thepump device 3205 a may be in the expanded state while the pump 3205 bmay be in the retracted state such that the pumps 3205 a and 3205 b arecollectively driving fluid through the pump system 3305 withoutinterruption.

A further advantage pump system 3250 or 3305 is that it may be used inconjunction with a passive reverse flow system which is configured toreturn blood to the central venous system, as is disclosed elsewhere inthis document. These two systems may share a venous return line, and areconnected by a valve or other flow control device.

The passive source of aspiration may be a site with lower pressure, forexample a sheath inserted into a central vein (for venous return) or anIV bag placed at a vertical level that would vary depending on whatamount of negative pressure is desired. FIG. 38 shows an exemplaryembodiment of a system 3500 that uses venous return to establish passiveretrograde flow into the arterial access device. The system 3500includes the arterial access device 3510, a venous return device 3515,and a flow line 3520 that provides a passageway for retrograde flow fromthe arterial access device 3510 to the venous return device 3515. A flowcontrol assembly 3525 interacts with the flow line 3520. The flowcontrol assembly 3525 is adapted to regulate and/or monitor theretrograde flow through the flow line 3520. The flow control assembly3525 interacts with the flow pathway through the flow line 3520 todetermine the state and level of flow through the flow line.

In an embodiment, the arterial access device 3510 at least partiallyinserts into the common carotid artery CCA and the venous return device3515 at least partially inserts into a venous return site, such as thefemoral vein or internal jugular vein, as described in more detailbelow. The venous return device 3515 can be inserted into the femoralvein FV via a percutaneous puncture in the groin. The arterial accessdevice 3510 and the venous return device 3515 couple to opposite ends ofthe flow line 3520 at connectors. The distal end of the arterial accessdevice 3510 with the occlusion element 3529 may be positioned in theICA. Alternately, in some circumstances where the ICA access isextremely tortuous, it may be preferable to position the occlusionelement more proximally in the common carotid artery. When flow throughthe internal carotid artery is blocked (using the occlusion element3529), the natural pressure gradient between the internal carotid arteryand the venous system causes blood to flow in a retrograde or reversedirection from the cerebral vasculature through the internal carotidartery and through the flow line 3520 into the venous system.

In another embodiment, the arterial access device 3510 accesses thecommon carotid artery CCA via a transcarotid approach while the venousreturn device 3515 access a venous return site other than the femoralvein, such as the internal jugular vein. In another embodiment, thesystem provides retrograde flow from the carotid artery to an externalreceptacle, for example an IV bag, rather than to a venous return site.The arterial access device 3510 connects to the receptacle via the flowline 3520, which communicates with the flow control assembly 3525. Theretrograde flow of blood is collected in the receptacle. If desired, theblood could be filtered and subsequently returned to the patient. Thepressure of the receptacle could be set at zero pressure (atmosphericpressure) or even lower, causing the blood to flow in a reversedirection from the cerebral vasculature to the receptacle.

Exemplary Embodiments of Thrombectomy Devices

FIG. 39 shows an exemplary embodiment of a thrombectomy device 15. In anembodiment, the device has been adapted for transcarotid access to thecerebral circulation. The device 15 includes an expandable member 3905on a pusher wire 3910. The expandable member can be loaded in anunexpanded state into a delivery microcatheter 3915 which has alreadybeen positioned at or across the occlusion. The expandable member 3905is advanced via pushing the pusher wire 3910 through the microcatheter3915 and across the occlusion. Once positioned, the microcatheter 3915is pulled back so that the expandable member 3905 can expand and engagethe occlusion. The adaption of this device for transcarotid accessmethod comprises shortening the working length of both the pusher wire3910 and microcatheter 3915 by between 60 and 90 cm from the workinglengths of devices adapted for transfemoral delivery. The thrombectomydevice 15 has a working length that allows it to extend out of thearterial access device 2010 or catheter 2030 with enough length toaccess and cross the cerebral occlusion. More specifically, thethrombectomy device 15 has a working length of between 80 and 120 cm.Additionally, this adaption may comprise reducing the lengths of thedistal flexible sections of the microcatheter 3915 to improve thedeliverability of the device to the target site. The thrombectomy device15 may be configured to remove an occlusion as a single piece by notbreaking the occlusion into multiple pieces. This may minimize oreliminate the creation of emboli distal to the location of the clot. Inan embodiment, once the expandable member 3905 is expanded at thelocation of the occlusion, the expandable member is maintained in thatlocation for a period of time in order to create a perfusion channelthrough the occlusion that causes the thrombus to be lysed by theresultant blood flow passing through the thrombus. In such anembodiment, it is possible but not necessary that the expandable member3905 capture a portion of the thrombus for retrieval outside thepatient. When a sufficient portion of the thrombus has been lysed tocreate a desired flow channel through the obstruction, or outrightremoval of the obstruction is achieved by the resultant blood flow, theexpandable member 3905 may be withdrawn into the catheter or accesssheath and subsequently removed from the patient. The expandable portionmay capture some or all of the thrombus while being withdrawn into thesheath.

It should be appreciated that other mechanical thrombectomy cathetersmay be used in a similar manner with the vascular access and reverseflow system as described above. Mechanical thrombectomy devices maycoil-tipped retrievers, stent retrievers, expandable cages, wire orfilament loops, graspers, brushes, or the like. These clot retrieversmay include aspiration lumens to lower the risk of embolic debrisleading to ischemic complications. Alternately, thrombectomy devices mayinclude clot disruption elements such as fluid vortices, ultrasound orlaser energy elements, balloons, or the like, coupled with flushing andaspiration to remove the thrombus. Some exemplary devices and methodsare described in the following U.S. Patents and Patent Publications,which are all incorporated by reference in their entirety: U.S. Pat.Nos. 6,663,650, 6,730,104; 6,428,531, 6,379,325, 6,481,439, 6,929,632,5,938,645, 6,824,545, 6,679,893, 6,685,722, 6,436,087, 5,794,629, U.S.Patent Pub. No. 20080177245, U.S. Patent Pub. No. 20090299393, U.S.Patent Pub. No. 20040133232, U.S. Patent Pub. No. 20020183783, U.S.Patent Pub. No. 20070198028, U.S. Patent Pub. No. 20060058836, U.S.Patent Pub. No. 20060058837, U.S. Patent Pub. No. 20060058838, U.S.Patent Pub. No. 20060058838, U.S. Patent Pub. No. 20030212384, and U.S.Patent Pub. No. 20020133111.

A major drawback to prior thrombectomy devices is the need to re-crossthe occlusion with a guidewire and microcatheter if the thrombectomydevice did not remove enough of the occlusion to restore adequate flow,and additional attempts are needed to remove the occlusion. Currently, asingle-lumen microcatheter is used to deliver the thrombectomy device.The microcatheter is placed over a guidewire, the guidewire is thenremoved and the thrombectomy device is delivered. When removing theocclusion both the microcatheter and device are pulled back and theaccess across the occlusion is lost. Thus if the attempt at removal wasunsuccessful or incomplete and an additional attempt is required, theguidewire and microcatheter must again cross the occlusion. As mentionedabove, this extra step of re-crossing the occlusion takes time andincurs risk of distal vessel injury. An embodiment of this disclosure,shown in FIG. 40, is a microcatheter 4200 which includes at least twolumens, one lumen for a guide wire 2515 and the second to deliver athrombectomy device 4100 such as a stentriever or coil retriever. Thepresence of a second lumen for the guide wire may add outer profile to amicrocatheter over a microcatheter with just a single lumen. However,the reduced time and risk that may be provided by a second guidewirelumen can be advantageous. In addition, for use transcarotidly, theguidewire and/or the catheter walls may be scaled down to be less thanconventional wall thicknesses, to lower the overall increase needed toadd the extra lumen.

Exemplary Embodiments of Perfusion Devices

In an embodiment, the system may include a way to perfuse the cerebralvasculature distal to the thrombotic blockage and ischemic brain tissuevia a perfusion catheter delivered, for example, through the arterialaccess device 2010 to a site distal to the thrombotic occlusion 10. Theperfusion catheter is adapted to deliver a perfusion solution to adesired location. Perfusion solution may include, for example,autologous arterial blood, either from the flow line of a passivereverse flow circuit 3500 or from another artery, oxygenated solution,or other neuroprotective agent. In addition, the perfusion solution maybe hypothermic to cool the brain tissue, another strategy which has beenshown to minimize brain injury during periods of ischemia. The perfusioncatheter may also be used to deliver a bolus of an intra-arterialthrombolytic agent pursuant to thrombolytic therapy. Typically,thrombolytic therapy may take up to 1-2 hours or more to clear ablockage after the bolus has been delivered. Mechanical thrombectomy mayalso take up to 1 to 2 hours to successfully recanalize the blockedartery. Distal perfusion of the ischemic region may minimize the levelof brain injury during the stroke treatment procedure. Embodiments ofdistal perfusion are described below.

FIG. 41 shows a perfusion catheter 3600 positioned across the thromboticblockage 10, to enable perfusion distal to the blockage. In anembodiment, the catheter is 3600 positioned over a guidewire placedthrough a lumen in the catheter. The lumen may serve as both a guidewirelumen and a perfusion lumen. Once placed, the guidewire may be removedto maximize the throughspace of the lumen available for perfusion.Alternately, the guidewire lumen and the perfusion lumen may be twoseparate lumens within the catheter, so that the guidewire may remain inplace in the guidewire lumen during perfusion without interfering withthe perfusion lumen. Perfusion exit holes 3615, which communicate withthe perfusion lumen, are located in a distal region of the catheter3600. This perfusion lumen may be connected to a perfusion source suchas a perfusion pump or syringe and may be used for perfusing fluid suchas neuroprotective agents and/or oxygenated blood such as the patient'sown arterial blood via the perfusion exit holes 3615 as exhibited by thearrows P in FIG. 41, which represent the flow of perfusion solution outof the catheter 3600. Alternately, the catheter 3600 may be positionedrelative to the blockage 10 such that the perfusion exit holes 3615 areinitially positioned just proximal to, or within, the thromboticblockage 10 during a bolus of thrombolytic infusion. The catheter canthen be re-positioned so that at least some of the perfusion exit holes3615 are located distal of the blockage 10 to provide distal perfusionwith blood or an equivalent solution to the ischemic penumbra. Theperfusion catheter may be used in conjunction with mechanical oraspiration thrombectomy as above. The catheter may be positioned throughthe lumen of access device 2010 or catheter 2030. The catheter may beplaced side by side with mechanical thrombectomy element in the lumen,or may be co-axial with mechanical thrombectomy device.

FIG. 42 shows another embodiment of a perfusion catheter 3600 with aperfusion lumen 3610 that communicates with side holes 3615 and/or anend opening 3616 for perfusing fluid, and a second lumen 3612 forpressure monitoring. The pressure monitoring lumen 3612 is closed off ata distal-most end 3613. A side opening 3614 to the lumen 3612 is locatedproximal of the distal-most end 3613 for measuring perfusion pressure.The catheter 3600 is shown without an expandable occlusion elementalthough it could include an expandable occlusion element such as anocclusion balloon. The occlusion element may be positioned either distalto or proximal to the side holes 3615. In an embodiment, the perfusionsource may be controlled by the perfusion pressure measurement tomaintain perfusion pressure below 200 mm Hg. In an embodiment, theperfusion flow rate is controlled to maintain perfusion in the range ofabout 50 ml/min to about 250 ml/min.

In an alternate embodiment, as shown in FIG. 43, distal perfusioncatheter 3700 includes an occlusion balloon 3705, with perfusion exitholes 3715 positioned distal to, and/or proximal to the occlusionballoon 3705. As with the previous embodiment, the perfusion catheter3700 may be used in conjunction with recanalization therapies such asthrombectomy devices, aspiration mechanism or intra-arterialthrombolytic infusion. The catheter 3700 is placed in the vasculature sothat the occlusion balloon 3705 is positioned distal to the blockage 10.The catheter 3700 may be configured to perfuse the region distal of theballoon 3705 with blood or equivalent, and the region proximal of theballoon 3705 with thrombolytic agents. In this regard, the catheter 3700may include separate perfusion lumens 3720 and 3725 that communicatewith separate perfusion exit holes, as shown in FIG. 44. Alternately, asshown in FIG. 45, the distal and proximal perfusion exit holes areconnected to the same perfusion lumen 3630, and regions both distal andproximal to the occlusion balloon are used to infuse blood or alternateperfusion solution. Not shown in either FIGS. 43 and 44 is a separatelumen for inflation and deflation of occlusion balloon 3705. This lumenmay be embedded into the wall of the catheter.

In another embodiment, as shown in FIG. 46, the expandable occlusiondevice 3705 is a dilatation balloon which may provide a dilatation forceon the thrombus while the catheter 3700 is perfusing the distalvasculature.

The perfusion catheter may also provide perfusion to aid in thrombusremoval. FIG. 47 shows a proximal perfusion catheter 3800 being deployeddistal of the occlusion via the arterial access device 2010 or catheter3401. The proximal perfusion catheter 3800 includes an expandableocclusion element 3829 such as an occlusion balloon. The proximalperfusion catheter 3800 also includes one or more perfusion exit holes3820 at a location proximal to the occlusion element 3829. The perfusionexit holes 3820 communicate with an internal perfusion lumen in theperfusion catheter 3800 for perfusion of fluid out through the perfusionexit holes 3820. With reference still to FIG. 46, the proximal perfusioncatheter 3800 is deployed into the vasculature via the arterial accessdevice so that the occlusion element 3829 of the perfusion catheter ispositioned and expanded distal to the thrombus 10 with the perfusionexit holes 3820 positioned proximal to the occlusion element 3829 anddistal to the thrombus 10. Such an arrangement provides back pressure toassist in removal of the thrombus 10. In addition, the occlusion element3829 serves as distal emboli protection. Any of a variety of perfusionfluids may be used including, for example, oxygenated blood,neuroprotection agents, thrombolytics, as well as other fluids, whichmay be adjusted to a desired temperature. The arterial access device2010 can be used for aspiration in the arrangement of FIG. 47. Thearterial access device 2010 may have occlusion balloon 2020 as well aspassive or active aspiration mechanisms. The perfusion catheterfacilitates removal of the thrombus into the arterial access device 2010and thence through the flow line 2025 and out of the patient.

In addition to providing pressure distal to the occlusion, the perfusionfluid from proximal perfusion catheter 3800 can supply blood to smallervessels (perforators) originating in or just proximal to the occlusion.The shaft of the perfusion catheter 3800 may also be used as a rail orconduit for delivery of a therapeutic device such as stentriever orthrombectomy device.

In an embodiment, the perfusion lumen and the guide wire lumen are twoseparate lumens, configured for example as in FIG. 42. In an alternateembodiment, the perfusion lumen of the perfusion catheter 3800 alsoserves as a guide wire lumen. In such an arrangement, a valve isdesirably located at the distal end opening of the perfusion/guide wirelumen. When the guide wire is pushed distally out of the distal endopening of the guide wire lumen, the guide wire opens the valve. Thevalve automatically closes when the guide wire is retracted proximallyback into the lumen. In this manner, the valve seals the distal endopening of the lumen after the guide wire is retracted. The valve canalso be a pressure relief valve such that if the perfusion pressure istoo high, the valve opens to release the pressure.

FIGS. 48A-48D show an exemplary method of use of proximal perfusioncatheter 3800. FIG. 48A shows an enlarged view of a guide wire 3912positioned across the thrombus 10 in a cerebral artery. In FIG. 48B, adistal region of the perfusion catheter 3800 has been positioned acrossthe thrombus 10 (via the guide wire 3912) with the unexpanded occlusionelement 3829 positioned distal of the thrombus 10. The guide wire 3912protrudes out of the distal end of the guide wire lumen of the perfusioncatheter 3800. In FIG. 48C, the guide wire is not shown as it has beenretracted back into the guide wire lumen of the perfusion catheter 3800.If the guide wire lumen also serves as a perfusion lumen for theperfusion catheter 3800, a distal valve 3916 (such as a duckbill valve)at the distal end of the guide wire/perfusion lumen has automaticallyclosed such that the lumen can now be used for perfusion via theperfusion exit holes 3820, as represented by the arrows P in FIG. 48C.When the occlusion element 3829 is unexpanded (as shown in FIG. 48C),the perfusion exit holes 3820 can be used to perfuse distally. In FIG.48D, the expandable occlusion element 3829 has been expanded in theartery. The perfusion exit holes 3820 can then be used for perfusionproximal of the occlusion element 3829, as represented by the arrows P1in FIG. 48D.

Perfusion catheters 3600 or 3800 may include an element for monitoringblood pressure. In an embodiment, the pressure monitoring element is adedicated internal lumen in the perfusion catheter 3600 or 3800, whereinthe lumen is fluid-filled and connected to a pressure transducer on theproximal end of the perfusion catheter. A pressure transducer on thecatheter itself may also be used. Alternately, a pressure measuringguide wire may be inserted through an internal lumen of the perfusioncatheter 3600 or 3800 to a location where pressure is to be monitored.

Alternatively, cerebral perfusion can include cerebral retroperfusion asdescribed by Frazee et al. This embodiment involves selectivecannulation and occlusion of the transverse sinuses via the internaljugular vein, and infusion of blood via the superior sagittal sinus tothe brain tissue, during treatment of ischemic stroke. The followingarticles, which are incorporated herein by reference in their entirety,described cerebral retroperfusion and are incorporated by reference intheir entirety: Frazee, J. G. and X. Luo (1999). “Retrograde transvenousperfusion.” Crit Care Clin 15(4): 777-88, vii.; and Frazee, J. G., X.Luo, et al. (1998). “Retrograde transvenous neuroperfusion: a back doortreatment for stroke.” Stroke 29(9): 1912-6. This perfusion, in additionto providing protection to the cerebral tissue, may also cause aretrograde flow gradient in the cerebral arteries. Used in conjunctionwith the system 100, a retroperfusion component may provide oxygen tobrain tissue, as well as aid in capture of embolic debris into thereverse flow line during recanalization of the thrombotic occlusion 10.

It should be appreciated that other perfusion catheters or systems maybe used with the system 100, for example those described by U.S. Pat.Nos. 6,435,189 and 6,295,990, which are incorporated by reference intheir entirety.

Exemplary Methods and Devices for Transcarotid Vessel Closure

Any type of closing element, including a self-closing element, asuture-based closing element, or a hydrostatic seal element, may bedeployed on or about the penetration in the wall of the common carotidartery prior to withdrawing the arterial access device 2010 at the endof the procedure. Described herein are vessel closure methods anddevices that have been specifically configured for transcarotid vesselclosure. The following U.S. patent applications, which are incorporatedherein by reference in their entirety, describe exemplary closuredevices and methods: U.S. Patent Publication No. 20100042118, entitled“Suture Delivery Device”, and U.S. Patent Publication No. 20100228269,entitled “Vessel Closure Clip Device”. Additional examples oftranscarotid vessel closure devices and methods are described in U.S.Provisional Application Ser. No. 61/994,623, filed May 16, 2014, whichis incorporated by reference herein in its entirety. U.S. ProvisionalApplication Ser. No. 62/074,964 entitled “Vessel Access and ClosureAssist System and Method” and filed Nov. 4, 2014 and U.S. patentapplication Ser. No. 12/540,341 entitled “Suture Closure Device” arealso incorporated herein by reference in their entirety.

The closing element may be deployed at or near the beginning of theprocedure in a step termed “pre-closure”, or, the closing element couldbe deployed as the sheath is being withdrawn. In an embodiment, vesselclosure can be accomplished by a suture-based blood vessel closuredevice. The suture-based vessel closure device can place one or moresutures across a vessel access site such that, when the suture ends aretied off after sheath removal, the stitch or stitches provide hemostasisto the access site. The sutures can be applied either prior to insertionof the procedural sheath through the arteriotomy or after removal of thesheath from the arteriotomy. The device can maintain temporaryhemostasis of the arteriotomy after placement of sutures but before andduring placement of a procedural sheath, if a pre-closure step us used,and can also maintain temporary hemostasis after withdrawal of theprocedural sheath but before tying off the suture. Some exemplarysuture-based blood vessel disclosure devices are described in thefollowing U.S. Patents, which are incorporated herein by reference intheir entirety: U.S. Pat. Nos. 6,562,052; 7,001,400; and 7,004,952.

In an embodiment, the system includes an ultrasound probe element, whichwhen used with an ultrasound imaging system is configured to identifythe desired site of carotid arterial access to determine that issuitable for percutaneous puncture, for example to verify that there isno vascular disease in the vessel. The probe will also visualizesurrounding anatomy such as the internal jugular vein, to ensure thataccess can be achieved without comprising these other structures. Inaddition, the probe may be used to visualize the access site aftervessel closure to verify that hemostasis has been achieved. If needed,the probe may be used to provide localized compression at the site ofthe puncture as needed to ensure hemostasis. For example, after vesselclosure the probe is used to image the closure site. If blood is seenflowing from the site, the probe is pressed down to compress the site.The user periodically relaxes the pressure on the probe to assess ifhemostasis has been achieved. If it has not, pressure is reapplied. Ifit has, the probe may be removed.

In an embodiment shown in FIG. 49 the arterial access system 2000includes devices to facilitate the delivery of a vessel closure deviceonto a blood vessel for closing the opening in the wall of the bloodvessel. In an embodiment, the system 2000 is packaged as a kit thatincludes a procedural introducer sheath 2200, a sheath dilator 2600, anintroducer guide wire 3000, and a vessel closure device delivery sheath2205. In an embodiment, the kit also includes a vessel closure deviceapplier. In an embodiment, the vessel closure device delivery system isconfigured for use in a transcarotid procedure performed at leastpartially on a blood vessel located in the neck of a patient, such asthe carotid arteries including the common carotid artery. FIG. 50 showsthe arterial access system 200 assembled for insertion over theguidewire 3000 into the artery.

Exemplary Methods of Use

As illustrated in FIG. 1, the arterial access device 2010 istranscarotidly introduced directly into the common carotid artery CCA ofthe patient. This may be done with a percutaneous puncture or a directcut-down. In the case of a puncture, ultrasound imaging may be used toaccurately make the initial arterial puncture. The arterial accessdevice 2010 is threaded through the vasculature such that the distal tipis positioned in the common carotid artery or the proximal or distalcervical, petrous, or cavernous portion of the internal carotid arteryICA. A removable proximal extension may be used to place the arterialaccess device 2010 under fluoroscopy without exposing the user's hand toradiation. U.S. Patent Publication No. 2011/0034986, filed Jul. 12,2010, describes exemplary embodiments of removable proximal extensionsand is incorporated herein by reference.

Once the arterial access device is positioned, a diagnostic angiogrammay be performed via a microcatheter which has been configured fortranscarotid access and which is placed through the arterial accessdevice. Diagnostic angiograms are performed throughout the procedure todetermine the progress of the procedure.

A catheter 2030 is placed through the arterial access device 2010 or theguide catheter 2105 and positioned such that the distal tip reaches thetreatment site. If desired, a coaxial system of devices comprising aguide wire, a microcatheter, and the catheter 2030 are inserted togetherthrough the arterial access device 2010 and advanced towards thetreatment site. Alternately, a tapered dilator with or without amicrocatheter tip may be substituted for the microcatheter. Alternately,a microcatheter and guide wire may be placed inside the tapered dilator.The removable proximal extension, if used, may be removed prior tointroduction of the telescoping devices, or the devices may be insertedthrough the removable proximal extension. The microcatheter, or tapereddilator, and guide wire are then advanced to access and cross thecerebral occlusion. The microcatheter or dilator may be used to performthe angiogram of the cerebral circulation proximal and distal to theocclusion. The microcatheter may also used as a rail to advance thecatheter.

Typically, the largest size catheter will be selected which is able tobe safely navigated to the occlusion, to maximize the force and luminalarea for aspiration of the occlusion. Aspiration is then initiatedthrough the catheter. This may be done manually, with an aspirationpump, or with another aspiration source, or via the flow controller asdescribed above. If the thrombus is too large or too strongly embeddedinto the vasculature such that it is not possible to remove theocclusion via aspiration alone, further steps are taken to remove theocclusion. A thrombectomy device 15 may be deployed through the arterialaccess device to remove the clot. During clot retrieval, passive oractive aspiration may be applied via the arterial access device, or theguide catheter to minimize or eliminate the amount of distal emboli.

If the catheter is unable to reach the treatment site, or if a secondarymore distal treatment site needs to be reached after removal of a firstocclusion, a second, smaller diameter catheter may be inserted throughthe first catheter, and positioned at the distal treatment site.Alternately, the first catheter may be removed and exchanged for thesecond catheter. A guidewire and/or microcatheter may be placed throughthe first catheter to facilitate the exchange.

If there is difficulty navigating the catheter of the desired size tothe treatment site, a device may be deployed distal to the site andexpanded to act as an anchor to aid in advancing the catheter as shownin FIGS. 26 and 27. If desirable, a second catheter may be used in atelescoping manner to create support for the first catheter to accessthe proximal face of the occlusion. Alternately, a tapered dilator asshown in FIG. 25A or FIG. 25B may be used in addition to or in place ofthe microcatheter to facilitate navigation of the catheter. The arterialaccess device 2010 and the catheter 2030 may be connected to an elementfor passive or active aspiration, as shown in FIGS. 32-34, or a flowcontroller 3400 as shown in FIG. 35. In one embodiment, the arterialaccess device 2010 is connected to passive aspiration and the catheter2030 is connected to active aspiration. In another embodiment, bothdevices are connected to active aspiration. During the procedure, theuser may open or close the connections to the passive and/or activeaspiration sources as desired.

At any time during the procedure, a balloon on the arterial accessdevice 2010 may be inflated at this point to reduce forward arterialpressure on the occlusion. The inflated balloon may also increase thestability of the arterial access in the vessel to increase the supportfor advancement of devices through the arterial access device.Additionally, the arterial access device 2010 or guide catheter 2015 maybe connected to passive or active aspiration as desired to provideembolic protection while not compromising perfusion of the brain. Thismay be accomplished by selective periods of reverse, stopped, andantegrade flow. At the conclusion of the procedure, the arterial accesssheath may be closed by methods as described previously. Ultrasound mayagain be employed, in this instance to ascertain and/or ensurehemostasis. If appropriate, the ultrasound probe may be used to applypressure at the access site until hemostasis is achieved.

In a variation of this procedure, a guide catheter 2105 is insertedthrough the arterial access device 2010 which has been previouslyinserted into the CCA, as shown in FIG. 3. In this scenario, the guidecatheter 2105 may be removed and cleared onto a table during theprocedure or may be exchanged for another size or type of catheter asneeded without loss of arterial access. In addition, there is no need toexchange the sheath at the conclusion of the procedure before utilizinga vessel closure device. The arterial access device 2010 may incorporatea proximal extension such that during the procedure there is limitedexposure of radiation to the users' hands. In an embodiment, theproximal extension is removable and is removed prior to closure of theaccess site with a vessel closure device.

In yet a further embodiment, the system is used to provide distalprotection and/or perfusion during the procedure. In this embodiment, aperfusion catheter is inserted through the arterial access device 2010or through the catheter 2030, and positioned across the lumen andinflated at a point distal to the occlusion. The perfusion catheter maybe connected to a perfusion pump to perfuse oxygenated blood orperfusion solution to the ischemic brain via a distal opening in theperfusion catheter. In an embodiment, the perfusion catheter is aballoon-tipped catheter. The balloon is inflated at a point distal tothe occlusion. This balloon acts to prevent emboli from progressingdistally during removal or recanalization of the occlusion. Theperfusion catheter may also be connected to a flush source to perfuseproximal to the occlusion balloon via proximal ports in the perfusioncatheter. This maneuver essentially provides a back pressure on theocclusion and may aid it its removal.

In the instance where there is also a carotid artery stenosis whichrequires treatment either before or after treatment of the cerebralocclusion, an angioplasty balloon or stent may be deployed in thestenosis via the introducer sheath. If embolic protection is desirableduring intervention of the carotid stenosis, the introducer sheath mayhave an occlusion balloon and a connection to a reverse flow line asshown in FIG. 38, and the CAS procedure may be conducted under reverseflow embolic protection as described in U.S. Pat. No. 8,157,760, whichis incorporated herein by reference. Alternately, the arterial accessdevice 2010 may have two occlusion balloons as shown in FIG. 12, with anopening to allow balloon angioplasty or stenting of the carotidstenosis, and subsequent introduction of devices such as a catheter intothe ICA and cerebral circulation for treatment of the cerebral orintracranial arteries.

In yet another method of use, a telescoping system as depicted in FIG.31A is used to access and aspirate a cerebral occlusion in a rapidfashion, from either a transfemoral or transcarotid access site. Apuncture is first formed in an artery at an arterial access site, and asheath guide wire is inserted into the artery. The arterial accessdevice with a tapered dilator are inserted into the artery over thesheath guide wire. For the carotid artery access method, the arterialaccess device, sheath and sheath guide wire are designed fortranscarotid access. The arterial access device 2820 is then advancedand the distal tip is positioned in the common or internal carotidartery. The sheath and guidewire are then removed. If the arterialaccess device has an occlusion element 2815, at any point in theprocedure the occlusion element may be inflated to occlude the common orinternal carotid artery to reduce the risk of distal emboli to cerebralvessels. A telescoping catheter 2830 is positioned through the lumen ofthe arterial access device to a target occlusion site. The catheter 2830may be pre-assembled with a guide wire to aid in positioning, andinserted as a system into the access device 2820. Alternately, the guidewire is placed first across the occlusion site and the catheter isback-loaded onto the guide wire and into the sheath. The catheter mayalso be pre-loaded onto a microcatheter or tapered inner member such asthat depicted in FIG. 8 or 9, and the system inserted into the accessdevice 2820 and thence into the carotid vasculature and advanced to theocclusion site. Once the catheter is positioned at the occlusion site,the overlap region and/or sealing element between the catheter and theaccess device provides a seal between the two devices. All internaldevices such as guidewires, microcatheters, or tapered inner members areremoved. Aspiration is applied to a side arm of the arterial accessdevice, for example via side arm 2027 as shown in FIG. 1. Aspiration maybe via a syringe, a pump, or other means as disclosed above. If theocclusion is soft enough, aspiration is sufficient to remove theocclusion through the catheter and arterial access device and into theaspiration device via a side arm 2027 on the arterial access device. Ifthe occlusion is too hard to be completely removed in this manner but is“corked” or otherwise caught into the distal end and/or distal lumen ofthe catheter 2830 via the aspiration force, the occlusion may be removedby pulling back on the catheter 2830. As this maneuver may increase therisk of distal emboli, it may be a desirable time to inflate theocclusion element 2815 on the access device as described above. Once theclot has been pulled completely into the lumen of the access device2820, the catheter 2830 may be removed rapidly from the access device2830. If the clot detaches from the catheter 2830 during this step, itmay be removed easily through the larger lumen of the arterial accessdevice via the side arm 2027. Because the clot may be protruding fromthe distal tip of the catheter by as much as several centimeters, theuser may want to pull the distal marker of the catheter severalcentimeters into the arterial access device before rapid removal of thecatheter.

This method provides speed and ease of use benefits over traditionalconfiguration wherein the aspiration is applied via a catheter which isinserted the entire length of the arterial access device. For thistraditional configuration, aspiration is applied directly to theproximal end of the catheter, and must be applied during the entire timethe catheter is being removed from the access device. Likewise thecatheter must be removed very slowly, otherwise there is risk that theclot is lost and either lodged back in the vasculature or in the accessdevice. In contrast, for the telescoping method, direct aspiration tothe occlusion may be applied via the arterial access device rather thanthe catheter, and therefore once the clot is entered into the accessdevice the catheter may be rapidly removed. This difference may halve oreven further reduce the time for each “pass” of an aspiration attempt.For many stroke procedures, more than one pass is required to completelyremove the occlusion Furthermore, the fact that the back half of theaspiration lumen is the larger lumen of the access device rather thanthe smaller lumen of the catheter makes aspiration more effective. Itwill be more likely that the clot can be suctioned without “corking” atthe tip or in the lumen of the catheter, and increase the rate ofaspiration into the aspiration device.

In a variation of this method, a stentriever or similar device may beused as an adjunct to aspiration to remove the occlusion. It may be usedinitially before placement of the catheter to provide immediateperfusion through the occlusion, may be used to help providecounter-traction and rail support during positioning of the catheter,may aid in dislodging the clot into the catheter, or some or all of theabove.

While this specification contains many specifics, these should not beconstrued as limitations on the scope of an invention that is claimed orof what may be claimed, but rather as descriptions of features specificto particular embodiments. Certain features that are described in thisspecification in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable sub-combination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a sub-combination or a variation of a sub-combination.Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. Therefore the spirit and scope of the appended claims shouldnot be limited to the description of the embodiments contained herein.

What is claimed is:
 1. An aspiration catheter system comprising: anaccess sheath comprising a tubular sheath body with a central lumenhaving an inner diameter, a proximal end and a distal opening, and aconnector operably connected with the sheath body and attachable to anaspiration line that connects to an aspiration source via the connector;and a catheter comprising a distal portion and a proximal tetherextending proximally from a point of attachment between the proximaltether and the distal portion, wherein the distal portion has a singleinner lumen, and wherein the catheter is configured to extend from afemoral access site to a carotid artery, wherein the catheter isconfigured to slide within the central lumen of the sheath body tochange the relative position of the catheter within the central lumenand provide for at least a portion of the distal portion to extendoutward from the distal opening of the sheath body such that an overlapregion is formed between the catheter and the access sheath, wherein anaspiration lumen is collectively formed by the single inner lumen of thecatheter and the central lumen of the access sheath, and wherein aproximal end region of the catheter comprises an inclined surfaceflaring outward in a proximal direction, wherein the inclined surface isformed in a thickened portion of the catheter wall that is sized tocontact the inner diameter of the central lumen to provide sealingsufficient to transmit aspiration force to a distal opening of thecatheter to capture a thrombus.
 2. The aspiration catheter system ofclaim 1, wherein the inclined surface is biased outward and compressibleagainst the inner diameter of the sheath.
 3. The aspiration cathetersystems of claim 1, wherein the access sheath has an outer diameterranging from about 6 Fr to about 8 Fr and the inner diameter of thecatheter is between about 0.058″ and about 0.072″ and wherein the innerdiameter of the central lumen of the sheath body is between about 0.074″and about 0.088″.
 4. The aspiration catheter system of claim 1, whereinthe sheath body of the access sheath has a length from about 90 cm toabout 120 cm.
 5. The aspiration catheter system of claim 1, furthercomprising the aspiration source comprising a syringe having a volume ofat least 30 cc, and wherein a flow rate of at least about 321 mL/min isestablished when an aspiration pressure through the aspiration lumen isapplied by the syringe.
 6. The aspiration catheter system of claim 1,wherein the catheter comprises a radiopaque marker near the proximal endregion and a radiopaque marker near the distal opening.
 7. Theaspiration catheter system of claim 1, wherein the point of attachmentis positioned within a transition zone that bridges a flexibility of theproximal tether to a flexibility of the catheter.
 8. The aspirationcatheter system of claim 7, wherein the proximal tether within thetransition zone comprises a flattened distal end region.
 9. Theaspiration catheter system of claim 7, wherein the proximal end regionof the catheter within the transition zone comprises a reinforcementstructure.
 10. The aspiration catheter system of claim 1, wherein theinclined surface forms a single compressible external surface feature.11. The aspiration catheter system of claim 1, wherein the proximal endregion having the inclined surface has a substantially uniform innerdiameter.
 12. The aspiration catheter system of claim 1, wherein theaccess sheath having the central lumen is a single-lumen access sheath.13. The aspiration catheter system of claim 1, wherein the inclinedsurface forms a sealing element positioned on the external surface of aproximal end of the catheter.
 14. An aspiration catheter systemcomprising: an access sheath comprising a tubular sheath body with acentral lumen having an inner diameter, a proximal end and a distalopening, and a connector operably connected with the sheath body andattachable to an aspiration line that connects to an aspiration sourcevia the connector; and a catheter comprising a distal portion and aproximal tether extending proximally from a point of attachment betweenthe proximal tether and the distal portion, wherein the distal portionhas a single inner lumen, and wherein the catheter is configured toextend from a femoral access site to a carotid artery, wherein thecatheter is configured to slide within the central lumen of the sheathbody to change the relative position of the catheter within the centrallumen and provide for at least a portion of the distal portion to extendoutward from the distal opening of the sheath body such that an overlapregion is formed between the catheter and the access sheath, wherein anaspiration lumen is collectively formed by the single inner lumen of thecatheter and the central lumen of the access sheath, and wherein aproximal end region of the catheter wall thickens to form an inclinedsurface that flares outward so as to increase the outer diameter of theproximal end region, the inclined surface being biased outward againstthe inner diameter of the sheath.
 15. The aspiration catheter system ofclaim 14, wherein the inclined surface forms a compressible externalsurface feature.
 16. The aspiration catheter system of claim 14, whereinthe catheter comprises a radiopaque marker near the proximal end regionand a radiopaque marker near the distal opening.
 17. The aspirationcatheter system of claim 14, wherein the point of attachment ispositioned within a transition zone that bridges a flexibility of theproximal tether to a flexibility of the catheter.
 18. The aspirationcatheter system of claim 17, wherein the proximal tether within thetransition zone comprises a flattened distal end region.
 19. Theaspiration catheter system of claim 17, wherein the proximal end regionof the catheter within the transition zone comprises a reinforcementstructure.
 20. The aspiration catheter system of claim 18, furthercomprising the aspiration source comprising a syringe having a volume ofat least 30 cc, and wherein a flow rate of at least about 321 mL/min isestablished when an aspiration pressure through the aspiration lumen isapplied by the syringe.
 21. The aspiration catheter system of claim 18,wherein the inclined surface forms a single compressible externalsurface feature.
 22. The aspiration catheter system of claim 18, whereinthe proximal end region having the inclined surface has a substantiallyuniform inner diameter.
 23. The aspiration catheter system of claim 18,wherein the access sheath having the central lumen is a single-lumenaccess sheath.
 24. The aspiration catheter system of claim 18, whereinthe inclined surface forms a sealing element positioned on the externalsurface of a proximal end of the catheter.